Understanding genetic variation - the value of systems biology.

Science.gov (United States)

Hütt, Marc-Thorsten

2014-04-01

Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. © 2013 The British Pharmacological Society.

The value of mechanistic biophysical information for systems-level understanding of complex biological processes such as cytokinesis.

Science.gov (United States)

Pollard, Thomas D

2014-12-02

This review illustrates the value of quantitative information including concentrations, kinetic constants and equilibrium constants in modeling and simulating complex biological processes. Although much has been learned about some biological systems without these parameter values, they greatly strengthen mechanistic accounts of dynamical systems. The analysis of muscle contraction is a classic example of the value of combining an inventory of the molecules, atomic structures of the molecules, kinetic constants for the reactions, reconstitutions with purified proteins and theoretical modeling to account for the contraction of whole muscles. A similar strategy is now being used to understand the mechanism of cytokinesis using fission yeast as a favorable model system. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Micro-separation toward systems biology.

Science.gov (United States)

Liu, Bi-Feng; Xu, Bo; Zhang, Guisen; Du, Wei; Luo, Qingming

2006-02-17

Current biology is experiencing transformation in logic or philosophy that forces us to reevaluate the concept of cell, tissue or entire organism as a collection of individual components. Systems biology that aims at understanding biological system at the systems level is an emerging research area, which involves interdisciplinary collaborations of life sciences, computational and mathematical sciences, systems engineering, and analytical technology, etc. For analytical chemistry, developing innovative methods to meet the requirement of systems biology represents new challenges as also opportunities and responsibility. In this review, systems biology-oriented micro-separation technologies are introduced for comprehensive profiling of genome, proteome and metabolome, characterization of biomolecules interaction and single cell analysis such as capillary electrophoresis, ultra-thin layer gel electrophoresis, micro-column liquid chromatography, and their multidimensional combinations, parallel integrations, microfabricated formats, and nano technology involvement. Future challenges and directions are also suggested.

Nutritional Systems Biology

DEFF Research Database (Denmark)

Jensen, Kasper

and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... biology research. The paper also shows as a proof-of-concept that a systems biology approach to diet is meaningful and demonstrates some basic principles on how to work with diet systematic. The second chapter of this thesis we developed the resource NutriChem v1.0. A foodchemical database linking...... sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...

Analyzing the Biology on the System Level

OpenAIRE

Tong, Wei

2016-01-01

Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology,...

Systems biology in critical-care nursing.

Science.gov (United States)

Schallom, Lynn; Thimmesch, Amanda R; Pierce, Janet D

2011-01-01

Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurse's ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

Ten questions about systems biology

DEFF Research Database (Denmark)

Joyner, Michael J; Pedersen, Bente K

2011-01-01

to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many......In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...

Ten questions about systems biology

DEFF Research Database (Denmark)

Joyner, Michael J; Pedersen, Bente K

2011-01-01

In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

DEFF Research Database (Denmark)

Green, Sara; Serban, Maria; Scholl, Raphael

2018-01-01

of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological...... strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties...

Inverse problems in systems biology

International Nuclear Information System (INIS)

Engl, Heinz W; Lu, James; Müller, Stefan; Flamm, Christoph; Schuster, Peter; Kügler, Philipp

2009-01-01

Systems biology is a new discipline built upon the premise that an understanding of how cells and organisms carry out their functions cannot be gained by looking at cellular components in isolation. Instead, consideration of the interplay between the parts of systems is indispensable for analyzing, modeling, and predicting systems' behavior. Studying biological processes under this premise, systems biology combines experimental techniques and computational methods in order to construct predictive models. Both in building and utilizing models of biological systems, inverse problems arise at several occasions, for example, (i) when experimental time series and steady state data are used to construct biochemical reaction networks, (ii) when model parameters are identified that capture underlying mechanisms or (iii) when desired qualitative behavior such as bistability or limit cycle oscillations is engineered by proper choices of parameter combinations. In this paper we review principles of the modeling process in systems biology and illustrate the ill-posedness and regularization of parameter identification problems in that context. Furthermore, we discuss the methodology of qualitative inverse problems and demonstrate how sparsity enforcing regularization allows the determination of key reaction mechanisms underlying the qualitative behavior. (topical review)

Quantum Effects in Biological Systems

CERN Document Server

2016-01-01

Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

Science.gov (United States)

Degrazio, Dominick

Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level. Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to recombinantly derived therapeutic biologics. Concerns associated with this transformation are becoming prominent, as therapeutic biologics are uncharacteristic to small-molecule drugs. Maintaining the stability of a therapeutic biologic is a combination of balancing intrinsic factors and external elements within the biologic's microenvironment. An important aspect of this balance is relegated to the overall compatibility of primary, parenteral container-closure systems with therapeutic biologics

Mammalian Synthetic Biology: Engineering Biological Systems.

Science.gov (United States)

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

Science.gov (United States)

Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Genome Scale Modeling in Systems Biology: Algorithms and Resources

Science.gov (United States)

Najafi, Ali; Bidkhori, Gholamreza; Bozorgmehr, Joseph H.; Koch, Ina; Masoudi-Nejad, Ali

2014-01-01

In recent years, in silico studies and trial simulations have complemented experimental procedures. A model is a description of a system, and a system is any collection of interrelated objects; an object, moreover, is some elemental unit upon which observations can be made but whose internal structure either does not exist or is ignored. Therefore, any network analysis approach is critical for successful quantitative modeling of biological systems. This review highlights some of most popular and important modeling algorithms, tools, and emerging standards for representing, simulating and analyzing cellular networks in five sections. Also, we try to show these concepts by means of simple example and proper images and graphs. Overall, systems biology aims for a holistic description and understanding of biological processes by an integration of analytical experimental approaches along with synthetic computational models. In fact, biological networks have been developed as a platform for integrating information from high to low-throughput experiments for the analysis of biological systems. We provide an overview of all processes used in modeling and simulating biological networks in such a way that they can become easily understandable for researchers with both biological and mathematical backgrounds. Consequently, given the complexity of generated experimental data and cellular networks, it is no surprise that researchers have turned to computer simulation and the development of more theory-based approaches to augment and assist in the development of a fully quantitative understanding of cellular dynamics. PMID:24822031

Seasonal allergic rhinitis and systems biology-oriented biomarker discovery

NARCIS (Netherlands)

Baars, E.W.; Nierop, A.F.M.; Savelkoul, H.F.J.

2015-01-01

There is an increasing interest in science and medicine in the systems approach. Instead of the reductionist approach that focuses on the physical and chemical properties of the individual components, systems biology aims to describe, understand, and explain from the complex biological systems

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

Science.gov (United States)

Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

2018-03-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

Omics/systems biology and cancer cachexia.

Science.gov (United States)

Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

2016-06-01

Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. Copyright © 2016. Published by Elsevier Ltd.

Understanding Biological Rates and their Temperature Dependence, from Enzymes to Ecosystems

Science.gov (United States)

Prentice, E.; Arcus, V. L.

2017-12-01

Temperature responses over various scales in biological systems follow a similar pattern; negative curvature results in an optimum temperature (Topt) for activity/growth/turnover, with decreases in rates on either side of Topt. Previously this downturn in rates at high temperatures has been attributed to enzyme denaturation, where a failing of the basic driving units of metabolism was used to describe curvature at the enzyme and organism level. However, recent developments in our understanding of the factors governing enzyme rates at different temperatures have guided a new understanding of the responses of biological systems. Enzymes catalyse reactions by driving the substrate through a high energy species, which is tightly bound to the enzyme. Macromolecular rate theory (MMRT) has recently been developed to account for the changes in the system brought about by this tight binding, specifically the change in the physical parameter heat capacity (ΔCǂp), and the effect this has on the temperature dependence of enzyme reactions. A negative ΔCǂp imparts the signature negative curvature to rates in the absence of denaturation, and finds that Topt, ΔCǂp and curvature are all correlated, placing constraints on biological systems. The simplest of cells comprise thousands of enzymatically catalysed reactions, functioning in series and in parallel in metabolic pathways to determine the overall growth rate of an organism. Intuitively, the temperature effects of enzymes play a role in determining the overall temperature dependence of an organism, in tandem with cellular level regulatory responses. However, the effect of individual Topt values and curvature on overall pathway behaviour is less apparent. Here, this is investigated in the context of MMRT through the in vitro characterisation of a six-step metabolic pathway to understand the steps in isolation and functioning in series. Pathway behaviour is found to be approximately an average of the properties of the

Biological Systems Thinking for Control Engineering Design

Directory of Open Access Journals (Sweden)

D. J. Murray-Smith

2004-01-01

Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

Industrial systems biology and its impact on synthetic biology of yeast cell factories

DEFF Research Database (Denmark)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-01-01

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

7th Annual Systems Biology Symposium: Systems Biology and Engineering

Energy Technology Data Exchange (ETDEWEB)

Galitski, Timothy P.

2008-04-01

Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

On the limitations of standard statistical modeling in biological systems: a full Bayesian approach for biology.

Science.gov (United States)

Gomez-Ramirez, Jaime; Sanz, Ricardo

2013-09-01

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. Copyright © 2013 Elsevier Ltd. All rights reserved.

What it takes to understand and cure a living system: computational systems biology and a systems biology-driven pharmacokinetics-pharmacodynamics platform

NARCIS (Netherlands)

Swat, Maciej; Kiełbasa, Szymon M.; Polak, Sebastian; Olivier, Brett; Bruggeman, Frank J.; Tulloch, Mark Quinton; Snoep, Jacky L.; Verhoeven, Arthur J.; Westerhoff, Hans V.

2011-01-01

The utility of model repositories is discussed in the context of systems biology (SB). It is shown how such repositories, and in particular their live versions, can be used for computational SB: we calculate the robustness of the yeast glycolytic network with respect to perturbations of one of its

Using biological networks to improve our understanding of infectious diseases

Directory of Open Access Journals (Sweden)

Nicola J. Mulder

2014-08-01

Full Text Available Infectious diseases are the leading cause of death, particularly in developing countries. Although many drugs are available for treating the most common infectious diseases, in many cases the mechanism of action of these drugs or even their targets in the pathogen remain unknown. In addition, the key factors or processes in pathogens that facilitate infection and disease progression are often not well understood. Since proteins do not work in isolation, understanding biological systems requires a better understanding of the interconnectivity between proteins in different pathways and processes, which includes both physical and other functional interactions. Such biological networks can be generated within organisms or between organisms sharing a common environment using experimental data and computational predictions. Though different data sources provide different levels of accuracy, confidence in interactions can be measured using interaction scores. Connections between interacting proteins in biological networks can be represented as graphs and edges, and thus studied using existing algorithms and tools from graph theory. There are many different applications of biological networks, and here we discuss three such applications, specifically applied to the infectious disease tuberculosis, with its causative agent Mycobacterium tuberculosis and host, Homo sapiens. The applications include the use of the networks for function prediction, comparison of networks for evolutionary studies, and the generation and use of host–pathogen interaction networks.

Metabolomics: Definitions and Significance in Systems Biology.

Science.gov (United States)

Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

2017-01-01

Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.

Science.gov (United States)

Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle

2018-05-09

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.

Biological and social understanding of human nature: biopolitical dimension

Directory of Open Access Journals (Sweden)

S. K. Kostiuchkov

2014-07-01

Full Text Available This paper examines the position of the biopolitical nature of man as a biosocial being given supplies of both the two spheres of life – natural, biological and social. The necessity of understanding of human nature, which by definition are bio-social importance of the approach to the definition of man as an integral, binary-konnotovanoyi of the «social individual – a species» which is characterized by symmetrical opposition – upposition social and biological. It was found that the main task of modern political science, and in particular bio-political studies presented appeals to rethink the political picture of the world in order to predict the development of a new order or a new chaos. Understanding the formation of a new global civilization worldview is today one of the most important problems, which is connected with the main problem of the modern world – the task of preserving life on the planet. It is concluded that the contradictions of human nature – between the biological and the social, physical and spiritual, universal and the particular, natural and artificial, rational and emotional – in today’s conditions are extremely sharp. The said situation requires more in-depth scientific analysis of human nature, the study of the structural level as human biosocial system.

Thermostability of biological systems: fundamentals, challenges, and quantification.

Science.gov (United States)

He, Xiaoming

2011-01-01

This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems.

Understanding Digital Learning from the Perspective of Systems Dynamics

Science.gov (United States)

Kok, Ayse

2009-01-01

The System Dynamics approach can be seen as a new way of understanding dynamical phenonema (natural, physical, biological, etc.) that occur in our daily lives taking into consideration not only single pairs of cause-effect variables, but the functioning of the system as a whole. This approach also provides the students with a new understanding in…

Systems Modelling and the Development of Coherent Understanding of Cell Biology

Science.gov (United States)

Verhoeff, Roald P.; Waarlo, Arend Jan; Boersma, Kerst Th.

2008-01-01

This article reports on educational design research concerning a learning and teaching strategy for cell biology in upper-secondary education introducing "systems modelling" as a key competence. The strategy consists of four modelling phases in which students subsequently develop models of free-living cells, a general two-dimensional model of…

Industrial systems biology and its impact on synthetic biology of yeast cell factories.

Science.gov (United States)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-06-01

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Towards the understanding of network information processing in biology

Science.gov (United States)

Singh, Vijay

Living organisms perform incredibly well in detecting a signal present in the environment. This information processing is achieved near optimally and quite reliably, even though the sources of signals are highly variable and complex. The work in the last few decades has given us a fair understanding of how individual signal processing units like neurons and cell receptors process signals, but the principles of collective information processing on biological networks are far from clear. Information processing in biological networks, like the brain, metabolic circuits, cellular-signaling circuits, etc., involves complex interactions among a large number of units (neurons, receptors). The combinatorially large number of states such a system can exist in makes it impossible to study these systems from the first principles, starting from the interactions between the basic units. The principles of collective information processing on such complex networks can be identified using coarse graining approaches. This could provide insights into the organization and function of complex biological networks. Here I study models of biological networks using continuum dynamics, renormalization, maximum likelihood estimation and information theory. Such coarse graining approaches identify features that are essential for certain processes performed by underlying biological networks. We find that long-range connections in the brain allow for global scale feature detection in a signal. These also suppress the noise and remove any gaps present in the signal. Hierarchical organization with long-range connections leads to large-scale connectivity at low synapse numbers. Time delays can be utilized to separate a mixture of signals with temporal scales. Our observations indicate that the rules in multivariate signal processing are quite different from traditional single unit signal processing.

Understanding the biological and environmental implications of nanomaterials

Science.gov (United States)

Lin, Sijie

quantified by UV-vis spectrophotometry and fitted with the Freundlich isothem. Effects of the adsorption of QDs on the photosynthetic activities of the algae are evaluated using O2 evolution and CO2 depletion assays, and the ecological impact of such adsorption is discussed. To understand the effects of nanomaterials on the cell membrane, nanoparticles (Au, TiO2, and QDs) of different surface charges and chemical compositions are introduced to HT-29 mammalian cells in Chapter 4. The polarization of the cell membrane is investigated using a FLIPR membrane potential kit. The phase of the cell membrane, in the presence of both positively and negatively charged nanoparticles, are examined using laurden, a lipophilic dye that serves as a molecular reporter on the fluidic or gel phase of the host membrane. To address the effects of nanomaterials on biological and ecological systems within the same context, Chapter 5 offers a first parallel comparison between mammalian and plant cell responses to nanomaterials. This study is conducted using a plant cell viability assay, complimented by bright field, fluorescence, and electron microscopy imaging. Discussions of this study are presented based on the hydrophobicity and solubility of C60(OH) 20 and of supramolecular complex C70-NOM, hydrophobicity and porous structure of the plant Allium cepa cell wall, and the amphiphilic structure and endocytosis of the plasma cell membrane of both Allium cepa and HT-29 cells. Chapter 6 summarizes and rationalizes results obtained from the entire dissertation research. Future work inspired by this research is presented at the end of the chapter. Specifically, this dissertation is structured to embody the following essential and complementary chapters: (1) Chapter 1: Literature review (2) Chapter 2: Nano-Eco interactions at the whole organism level; (3) Chapter 3: Nano-Eco interactions at the cellular level; (4) Chapter 4: Nano-Bio interactions at the cellular level; (5) Chapter 5: Parallel comparison

Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

Directory of Open Access Journals (Sweden)

Ina Aretz

2016-04-01

Full Text Available Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

Science.gov (United States)

Aretz, Ina; Meierhofer, David

2016-04-27

Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

Synthetic Biology: Engineering Living Systems from Biophysical Principles.

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Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

2017-03-28

Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Sensitivity analysis approaches applied to systems biology models.

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Zi, Z

2011-11-01

With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

Towards a systems understanding of plant-microbe interactions

Directory of Open Access Journals (Sweden)

Akira eMine

2014-08-01

Full Text Available Plants are closely associated with microorganisms including pathogens and mutualists that influence plant fitness. Molecular genetic approaches have uncovered a number of signaling components from both plants and microbes and their mode of actions. However, signaling pathways are highly interconnected and influenced by diverse sets of environmental factors. Therefore, it is important to have systems views in order to understand the true nature of plant-microbe interactions. Indeed, systems biology approaches have revealed previously overlooked or misinterpreted properties of the plant immune signaling network. Experimental reconstruction of biological networks using exhaustive combinatorial mutants is particularly powerful to elucidate network structure and properties and relationships among network components. Recent advances in metagenomics of microbial communities associated with plants further point to the importance of systems approaches and open a research area of microbial community reconstruction. In this review, we highlight the importance of a systems understanding of plant-microbe interactions, with a special emphasis on reconstruction strategies.

Strategies for structuring interdisciplinary education in Systems Biology: an European perspective

NARCIS (Netherlands)

Cvijovic, Marija; Höfer, Thomas; Acimovic, Jure; Alberghina, Lilia; Almaas, Eivind; Besozzi, Daniela; Blomberg, Anders; Bretschneider, Till; Cascante, Marta; Collin, Olivier; Atauri, de Pedro; Depner, Cornelia; Dickinson, Robert; Dobrzynski, Maciej; Fleck, C.; Garcia-Ojalvo, Jordi; Gonze, Didier; Hahn, Jens; Hess, Heide Marie; Hollmann, Susanne; Krantz, Marcus; Kummer, Ursula; Lundh, Torbjörn; Martial, Gifta; Martins dos Santos, V.A.P.; Mauer-Oberthür, Angela; Regierer, Babette; Skene, Barbara; Stalidzans, Egils; Stelling, Jörg; Teusink, Bas; Workman, Christopher T.; Hohmann, Stefan

2016-01-01

Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological

Integrative systems and synthetic biology of cell-matrix adhesion sites.

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Zamir, Eli

2016-09-02

The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

Advancing metabolic engineering through systems biology of industrial microorganisms

DEFF Research Database (Denmark)

Dai, Zongjie; Nielsen, Jens

2015-01-01

resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

Dietary antioxidant synergy in chemical and biological systems.

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Wang, Sunan; Zhu, Fan

2017-07-24

Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

Tracing organizing principles: Learning from the history of systems biology

DEFF Research Database (Denmark)

Green, Sara; Wolkenhauer, Olaf

2014-01-01

on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational......With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...

The role of mechanics in biological and bio-inspired systems.

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Egan, Paul; Sinko, Robert; LeDuc, Philip R; Keten, Sinan

2015-07-06

Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

Advancing metabolic engineering through systems biology of industrial microorganisms.

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Dai, Zongjie; Nielsen, Jens

2015-12-01

Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances in Structural Biology and the Application to Biological Filament Systems.

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Popp, David; Koh, Fujiet; Scipion, Clement P M; Ghoshdastider, Umesh; Narita, Akihiro; Holmes, Kenneth C; Robinson, Robert C

2018-04-01

Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources (microfocus synchrotron beamlines and free electron lasers) and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. We assemble a model of a capped tropomyosin-actin minifilament to demonstrate the utility of combining structures determined by different techniques. Finally, we survey the methods that attempt to transform high resolution structural biology into more physiological environments, such as the cell. Together these techniques promise a compelling decade for structural biology and, more importantly, they will provide exciting discoveries in understanding the designs and purposes of biological machines. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Integrative radiation systems biology

International Nuclear Information System (INIS)

Unger, Kristian

2014-01-01

Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

Feedback dynamics and cell function: Why systems biology is called Systems Biology.

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Wolkenhauer, Olaf; Mesarovic, Mihajlo

2005-05-01

A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

Using multi-criteria analysis of simulation models to understand complex biological systems

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Maureen C. Kennedy; E. David. Ford

2011-01-01

Scientists frequently use computer-simulation models to help solve complex biological problems. Typically, such models are highly integrated, they produce multiple outputs, and standard methods of model analysis are ill suited for evaluating them. We show how multi-criteria optimization with Pareto optimality allows for model outputs to be compared to multiple system...

On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

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Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

2017-12-05

The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

Systems Biology Knowledgebase for a New Era in Biology A Genomics:GTL Report from the May 2008 Workshop

Energy Technology Data Exchange (ETDEWEB)

Gregurick, S.; Fredrickson, J. K.; Stevens, R.

2009-03-01

Biology has entered a systems-science era with the goal to establish a predictive understanding of the mechanisms of cellular function and the interactions of biological systems with their environment and with each other. Vast amounts of data on the composition, physiology, and function of complex biological systems and their natural environments are emerging from new analytical technologies. Effectively exploiting these data requires developing a new generation of capabilities for analyzing and managing the information. By revealing the core principles and processes conserved in collective genomes across all biology and by enabling insights into the interplay between an organism's genotype and its environment, systems biology will allow scientific breakthroughs in our ability to project behaviors of natural systems and to manipulate and engineer managed systems. These breakthroughs will benefit Department of Energy (DOE) missions in energy security, climate protection, and environmental remediation.

Effect of Process-Oriented Guided-Inquiry Learning on Non-majors Biology Students' Understanding of Biological Classification

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Wozniak, Breann M.

The purpose of this study was to examine the effect of process-oriented guided-inquiry learning (POGIL) on non-majors college biology students' understanding of biological classification. This study addressed an area of science instruction, POGIL in the non-majors college biology laboratory, which has yet to be qualitatively and quantitatively researched. A concurrent triangulation mixed methods approach was used. Students' understanding of biological classification was measured in two areas: scores on pre and posttests (consisting of 11 multiple choice questions), and conceptions of classification as elicited in pre and post interviews and instructor reflections. Participants were Minnesota State University, Mankato students enrolled in BIOL 100 Summer Session. One section was taught with the traditional curriculum (n = 6) and the other section in the POGIL curriculum (n = 10) developed by the researcher. Three students from each section were selected to take part in pre and post interviews. There were no significant differences within each teaching method (p familiar animal categories and aquatic habitats, unfamiliar organisms, combining and subdividing initial groupings, and the hierarchical nature of classification. The POGIL students were the only group to surpass these challenges after the teaching intervention. This study shows that POGIL is an effective technique at eliciting students' misconceptions, and addressing these misconceptions, leading to an increase in student understanding of biological classification.

Proteomics Improves the New Understanding of Honeybee Biology.

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Hora, Zewdu Ararso; Altaye, Solomon Zewdu; Wubie, Abebe Jemberie; Li, Jianke

2018-04-11

The honeybee is one of the most valuable insect pollinators, playing a key role in pollinating wild vegetation and agricultural crops, with significant contribution to the world's food production. Although honeybees have long been studied as model for social evolution, honeybee biology at the molecular level remained poorly understood until the year 2006. With the availability of the honeybee genome sequence and technological advancements in protein separation, mass spectrometry, and bioinformatics, aspects of honeybee biology such as developmental biology, physiology, behavior, neurobiology, and immunology have been explored to new depths at molecular and biochemical levels. This Review comprehensively summarizes the recent progress in honeybee biology using proteomics to study developmental physiology, task transition, and physiological changes in some of the organs, tissues, and cells based on achievements from the authors' laboratory in this field. The research advances of honeybee proteomics provide new insights for understanding of honeybee biology and future research directions.

Toward High School Biology: Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems.

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Herrmann-Abell, Cari F; Koppal, Mary; Roseman, Jo Ellen

2016-01-01

Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better foundation, we used research-based design principles and collaborated in the development of a curricular intervention that applies chemistry ideas to living and nonliving contexts. Six eighth grade teachers and their students participated in a test of the unit during the Spring of 2013. Two of the teachers had used an earlier version of the unit the previous spring. The other four teachers were randomly assigned either to implement the unit or to continue teaching the same content using existing materials. Pre- and posttests were administered, and the data were analyzed using Rasch modeling and hierarchical linear modeling. The results showed that, when controlling for pretest score, gender, language, and ethnicity, students who used the curricular intervention performed better on the posttest than the students using existing materials. Additionally, students who participated in the intervention held fewer misconceptions. These results demonstrate the unit's promise in improving students' understanding of the targeted ideas. © 2016 C. F. Herrmann-Abell et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Mapping biological systems to network systems

CERN Document Server

Rathore, Heena

2016-01-01

The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

Towards a Unified Understanding of Lithium Action in Basic Biology and its Significance for Applied Biology.

Science.gov (United States)

Jakobsson, Eric; Argüello-Miranda, Orlando; Chiu, See-Wing; Fazal, Zeeshan; Kruczek, James; Nunez-Corrales, Santiago; Pandit, Sagar; Pritchet, Laura

2017-12-01

Lithium has literally been everywhere forever, since it is one of the three elements created in the Big Bang. Lithium concentration in rocks, soil, and fresh water is highly variable from place to place, and has varied widely in specific regions over evolutionary and geologic time. The biological effects of lithium are many and varied. Based on experiments in which animals are deprived of lithium, lithium is an essential nutrient. At the other extreme, at lithium ingestion sufficient to raise blood concentration significantly over 1 mM/, lithium is acutely toxic. There is no consensus regarding optimum levels of lithium intake for populations or individuals-with the single exception that lithium is a generally accepted first-line therapy for bipolar disorder, and specific dosage guidelines for sufferers of that condition are generally agreed on. Epidemiological evidence correlating various markers of social dysfunction and disease vs. lithium level in drinking water suggest benefits of moderately elevated lithium compared to average levels of lithium intake. In contrast to other biologically significant ions, lithium is unusual in not having its concentration in fluids of multicellular animals closely regulated. For hydrogen ions, sodium ions, potassium ions, calcium ions, chloride ions, and magnesium ions, blood and extracellular fluid concentrations are closely and necessarily regulated by systems of highly selective channels, and primary and secondary active transporters. Lithium, while having strong biological activity, is tolerated over body fluid concentrations ranging over many orders of magnitude. The lack of biological regulation of lithium appears due to lack of lithium-specific binding sites and selectivity filters. Rather lithium exerts its myriad physiological and biochemical effects by competing for macromolecular sites that are relatively specific for other cations, most especially for sodium and magnesium. This review will consider what is known

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

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Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

Agent-Based Modeling in Molecular Systems Biology.

Science.gov (United States)

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-06-08

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Geochemistry and the Understanding of Groundwater Systems

Science.gov (United States)

Glynn, P. D.; Plummer, L. N.; Weissmann, G. S.; Stute, M.

2009-12-01

Geochemical techniques and concepts have made major contributions to the understanding of groundwater systems. Advances continue to be made through (1) development of measurement and characterization techniques, (2) improvements in computer technology, networks and numerical modeling, (3) investigation of coupled geologic, hydrologic, geochemical and biologic processes, and (4) scaling of individual observations, processes or subsystem models into larger coherent model frameworks. Many applications benefit from progress in these areas, such as: (1) understanding paleoenvironments, in particular paleoclimate, through the use of groundwater archives, (2) assessing the sustainability (recharge and depletion) of groundwater resources, and (3) their vulnerability to contamination, (4) evaluating the capacity and consequences of subsurface waste isolation (e.g. geologic carbon sequestration, nuclear and chemical waste disposal), (5) assessing the potential for mitigation/transformation of anthropogenic contaminants in groundwater systems, and (6) understanding the effect of groundwater lag times in ecosystem-scale responses to natural events, land-use changes, human impacts, and remediation efforts. Obtaining “representative” groundwater samples is difficult and progress in obtaining “representative” samples, or interpreting them, requires new techniques in characterizing groundwater system heterogeneity. Better characterization and simulation of groundwater system heterogeneity (both physical and geochemical) is critical to interpreting the meaning of groundwater “ages”; to understanding and predicting groundwater flow, solute transport, and geochemical evolution; and to quantifying groundwater recharge and discharge processes. Research advances will also come from greater use and progress (1) in the application of environmental tracers to ground water dating and in the analysis of new geochemical tracers (e.g. compound specific isotopic analyses, noble gas

Computational Systems Chemical Biology

OpenAIRE

Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

2011-01-01

There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

Next-Generation Sequencing: From Understanding Biology to Personalized Medicine

Directory of Open Access Journals (Sweden)

Benjamin Meder

2013-03-01

Full Text Available Within just a few years, the new methods for high-throughput next-generation sequencing have generated completely novel insights into the heritability and pathophysiology of human disease. In this review, we wish to highlight the benefits of the current state-of-the-art sequencing technologies for genetic and epigenetic research. We illustrate how these technologies help to constantly improve our understanding of genetic mechanisms in biological systems and summarize the progress made so far. This can be exemplified by the case of heritable heart muscle diseases, so-called cardiomyopathies. Here, next-generation sequencing is able to identify novel disease genes, and first clinical applications demonstrate the successful translation of this technology into personalized patient care.

Systems Biology of Saccharomyces cerevisiae Physiology and its DNA Damage Response

DEFF Research Database (Denmark)

Fazio, Alessandro

The yeast Saccharomyces cerevisiae is a model organism in biology, being widely used in fundamental research, the first eukaryotic organism to be fully sequenced and the platform for the development of many genomics techniques. Therefore, it is not surprising that S. cerevisiae has also been widely...... used in the field of systems biology during the last decade. This thesis investigates S. cerevisiae growth physiology and DNA damage response by using a systems biology approach. Elucidation of the relationship between growth rate and gene expression is important to understand the mechanisms regulating...... set of growth dependent genes by using a multi-factorial experimental design. Moreover, new insights into the metabolic response and transcriptional regulation of these genes have been provided by using systems biology tools (Chapter 3). One of the prerequisite of systems biology should...

Carbon nanomaterials in biological systems

Energy Technology Data Exchange (ETDEWEB)

Pu Chun Ke [Laboratory of Single-Molecule Biophysics and Polymer Physics, Department of Physics and Astronomy, Clemson University, Clemson, SC 29634 (United States); Qiao Rui [Department of Mechanical Engineering, Clemson University, Clemson, SC 29634 (United States)

2007-09-19

This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment. (topical review)

Carbon nanomaterials in biological systems

International Nuclear Information System (INIS)

Pu Chun Ke; Qiao Rui

2007-01-01

This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment. (topical review)

Recent developments in systems biology and metabolic engineering of plant microbe interactions

Directory of Open Access Journals (Sweden)

Vishal Kumar

2016-09-01

Full Text Available Microorganisms play a crucial role in the sustainability of the various ecosystems. The characterization of various interactions between microorganisms and other biotic factors is a necessary footstep to understand the association and functions of microbial communities. Among the different microbial interactions in an ecosystem, plant-microbe interaction plays an important role to balance the ecosystem. The present review explores plant microbe interactions using gene editing and system biology tools towards the comprehension in improvement of plant traits. Further, system biology tools like FBA, OptKnock and constrain based modeling helps in understanding such interactions as a whole. In addition, various gene editing tools have been summarized and a strategy has been hypothesized for the development of disease free plants. Furthermore, we have tried to summarize the predictions through data retrieved from various types of sources such as high throughput sequencing data (e.g. single nucleotide polymorphism (SNP detection, RNA-seq, proteomics and metabolic models have been reconstructed from such sequences for species communities. It is well known fact that systems biology approaches and modeling of biological networks will enable us to learn the insight of such network and will also help further in understanding these interactions.

From systems biology to systems biomedicine.

Science.gov (United States)

Antony, Paul M A; Balling, Rudi; Vlassis, Nikos

2012-08-01

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Systems Biology and Health Systems Complexity in;

NARCIS (Netherlands)

Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

2016-01-01

Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

Toward High School Biology: Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems

Science.gov (United States)

Herrmann-Abell, Cari F.; Koppal, Mary; Roseman, Jo Ellen

2016-01-01

Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better foundation, we used research-based design principles and collaborated in the development of a curricular intervention that applies chemistry ideas to living and nonliving contexts. Six eighth grade teachers and their students participated in a test of the unit during the Spring of 2013. Two of the teachers had used an earlier version of the unit the previous spring. The other four teachers were randomly assigned either to implement the unit or to continue teaching the same content using existing materials. Pre- and posttests were administered, and the data were analyzed using Rasch modeling and hierarchical linear modeling. The results showed that, when controlling for pretest score, gender, language, and ethnicity, students who used the curricular intervention performed better on the posttest than the students using existing materials. Additionally, students who participated in the intervention held fewer misconceptions. These results demonstrate the unit’s promise in improving students’ understanding of the targeted ideas. PMID:27909024

Epistemological Predictors of Prospective Biology Teachers' Nature of Science Understandings

Science.gov (United States)

Köseoglu, Pinar; Köksal, Mustafa Serdar

2015-01-01

The purpose of this study was to investigate epistemological predictors of nature of science understandings of 281 prospective biology teachers surveyed using the Epistemological Beliefs Scale Regarding Science and the Nature of Science Scale. The findings on multiple linear regression showed that understandings about definition of science and…

Interactive analysis of systems biology molecular expression data

Directory of Open Access Journals (Sweden)

Prabhakar Sunil

2008-02-01

Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

A CRISPR-based MLST Scheme for Understanding the Population Biology and Epidemiology of Salmonella Enterica

Science.gov (United States)

2015-05-26

N. Shariat, R. E. Timme, J. B. Pettengill, R. Barrangou, E. G. Dudley. Characterization and evolution of Salmonella CRISPR - Cas systems...Barrangou, Edward G. Dudley. Characterization of CRISPR - Cas in Salmonella, 3rd European CRISPR meeting. 14-MAY-14, . : , Margaret K. Kirchner, Nikki... CRISPRs Beyond subtyping approaches, we were motivated to understand the biology of CRISPR - Cas systems in Salmonella. We performed in-depth sequence

Carbon-13 NMR spectroscopy of biological systems

CERN Document Server

Beckmann, Nicolau

1995-01-01

This book is intended to provide an in-depth understanding of 13C NMR as a tool in biological research. 13C NMR has provided unique information concerning complex biological systems, from proteins and nucleic acids to animals and humans. The subjects addressed include multidimensional heteronuclear techniques for structural studies of molecules in the liquid and solid states, the investigation of interactions in model membranes, the elucidation of metabolic pathwaysin vitro and in vivo on animals, and noninvasive metabolic studies performed on humans. The book is a unique mix of NMR methods and biological applications which makes it a convenient reference for those interested in research in this interdisciplinary area of physics, chemistry, biology, and medicine.Key Features* An interdisciplinary text with emphasis on both 13C NMR methodology and the relevant biological and biomedical issues* State-of-the-art 13C NMR techniques are described; Whenever possible, their advantages over other approaches are empha...

Glycoengineering in CHO cells: Advances in systems biology

DEFF Research Database (Denmark)

Tejwani, Vijay; Andersen, Mikael Rørdam; Nam, Jong Hyun

2018-01-01

are not well understood. A systems biology approach combining different technologies is needed for complete understanding of the molecular processes accounting for this variability and to open up new venues in cell line development. In this review, we describe several advances in genetic manipulation, modeling......For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis....... Recently, CHO cells have also been explored for production of therapeutic glycosaminoglycans (e.g. heparin), which presents similar challenges as producing glycoproteins biologics. Approaches to controlling heterogeneity in CHO cells and directing the biosynthetic process toward desired glycoforms...

ADAM: analysis of discrete models of biological systems using computer algebra.

Science.gov (United States)

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web

The mammary gland in domestic ruminants: a systems biology perspective.

Science.gov (United States)

Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

2013-12-06

Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

Biological conversion system

Science.gov (United States)

Scott, C.D.

A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

Biocellion: accelerating computer simulation of multicellular biological system models.

Science.gov (United States)

Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

2014-11-01

Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Development trend of radiation biology research-systems radiation biology

International Nuclear Information System (INIS)

Min Rui

2010-01-01

Radiation biology research has past 80 years. We have known much more about fundamentals, processes and results of biology effects induced by radiation and various factors that influence biology effects wide and deep, however many old and new scientific problems occurring in the field of radiation biology research remain to be illustrated. To explore and figure these scientific problems need systemic concept, methods and multi dimension view on the base of considerations of complexity of biology system, diversity of biology response, temporal and spatial process of biological effects during occurrence, and complex feed back network of biological regulations. (authors)

Systems biology: the reincarnation of systems theory applied in biology?

Science.gov (United States)

Wolkenhauer, O

2001-09-01

With the availability of quantitative data on the transcriptome and proteome level, there is an increasing interest in formal mathematical models of gene expression and regulation. International conferences, research institutes and research groups concerned with systems biology have appeared in recent years and systems theory, the study of organisation and behaviour per se, is indeed a natural conceptual framework for such a task. This is, however, not the first time that systems theory has been applied in modelling cellular processes. Notably in the 1960s systems theory and biology enjoyed considerable interest among eminent scientists, mathematicians and engineers. Why did these early attempts vanish from research agendas? Here we shall review the domain of systems theory, its application to biology and the lessons that can be learned from the work of Robert Rosen. Rosen emerged from the early developments in the 1960s as a main critic but also developed a new alternative perspective to living systems, a concept that deserves a fresh look in the post-genome era of bioinformatics.

A Thai pre-service teacher's understanding of nature of science in biology teaching

Science.gov (United States)

Srisawat, Akkarawat; Aiemsum-ang, Napapan; Yuenyong, Chokchai

2018-01-01

This study was conducted on the effect of understanding and instruction of the nature of science of Ms. Wanida, a pre-service student under science education program in biology, Faculty of Education, Khon Kaen University. Wanida was a teaching practicum student majoring in biology at Khon Kaen University Demonstration School (Modindaeng). She was teaching biology for 38 Grade 10 students. Methodology regarded interpretive paradigm. The study aimed to examine 1) Wanida's understanding of the nature of science, 2) Wanida's instruction of the nature of science, 3 students' understanding of the nature of science from Wanida's instruction, and 4) the effects of Wanida's understanding and instruction of the nature of science on students' understanding of the nature of science from Wanida's instruction. Tools of interpretation included teaching observation, a semi-structured interview, open-ended questionnaire, and an observation record form for the instruction of the nature of science. The data obtained was interpreted, encoded, and classified, using the descriptive statistics. The findings indicated that Wanida held good understanding of the nature of science. She could apply the deficient nature of science approach mostly, followed by the implicit nature of science approach. Unfortunately, she could not show her teaching as explicit nature of science. However, her students' the understanding of the nature of science was good.

Advances in reproductive biology and seed production systems of ...

African Journals Online (AJOL)

Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this ...

An Integrative Systems Biology Approach to Understanding Pulmonary Diseases

NARCIS (Netherlands)

Auffray, Charles; Adcock, Ian M.; Chung, Kian Fan; Djukanovic, Ratko; Pison, Christophe; Sterk, Peter J.

2010-01-01

Chronic inflammatory pulmonary diseases such as COPD and asthma are highly prevalent and associated with a major health burden worldwide. Despite a wealth of biologic and clinical information on normal and pathologic airway structure and function, the primary causes and mechanisms of disease remain

Perspectives of a systems biology of the brain: the big data conundrum understanding psychiatric diseases.

Science.gov (United States)

Mewes, H W

2013-05-01

Psychiatric diseases provoke human tragedies. Asocial behaviour, mood imbalance, uncontrolled affect, and cognitive malfunction are the price for the biological and social complexity of neurobiology. To understand the etiology and to influence the onset and progress of mental diseases remains of upmost importance, but despite the much improved care for the patients, more then 100 years of research have not succeeded to understand the basic disease mechanisms and enabling rationale treatment. With the advent of the genome based technologies, much hope has been created to join the various dimension of -omics data to uncover the secrets of mental illness. Big Data as generated by -omics do not come with explanations. In this essay, I will discuss the inherent, not well understood methodological foundations and problems that seriously obstacle in striving for a quick success and may render lucky strikes impossible. © Georg Thieme Verlag KG Stuttgart · New York.

Inverse Problems in Systems Biology: A Critical Review.

Science.gov (United States)

Guzzi, Rodolfo; Colombo, Teresa; Paci, Paola

2018-01-01

Systems Biology may be assimilated to a symbiotic cyclic interplaying between the forward and inverse problems. Computational models need to be continuously refined through experiments and in turn they help us to make limited experimental resources more efficient. Every time one does an experiment we know that there will be some noise that can disrupt our measurements. Despite the noise certainly is a problem, the inverse problems already involve the inference of missing information, even if the data is entirely reliable. So the addition of a certain limited noise does not fundamentally change the situation but can be used to solve the so-called ill-posed problem, as defined by Hadamard. It can be seen as an extra source of information. Recent studies have shown that complex systems, among others the systems biology, are poorly constrained and ill-conditioned because it is difficult to use experimental data to fully estimate their parameters. For these reasons was born the concept of sloppy models, a sequence of models of increasing complexity that become sloppy in the limit of microscopic accuracy. Furthermore the concept of sloppy models contains also the concept of un-identifiability, because the models are characterized by many parameters that are poorly constrained by experimental data. Then a strategy needs to be designed to infer, analyze, and understand biological systems. The aim of this work is to provide a critical review to the inverse problems in systems biology defining a strategy to determine the minimal set of information needed to overcome the problems arising from dynamic biological models that generally may have many unknown, non-measurable parameters.

Context dependence of students' views about the role of equations in understanding biology.

Science.gov (United States)

Watkins, Jessica; Elby, Andrew

2013-06-01

Students' epistemological views about biology--their ideas about what "counts" as learning and understanding biology--play a role in how they approach their courses and respond to reforms. As introductory biology courses incorporate more physics and quantitative reasoning, student attitudes about the role of equations in biology become especially relevant. However, as documented in research in physics education, students' epistemologies are not always stable and fixed entities; they can be dynamic and context-dependent. In this paper, we examine an interview with an introductory student in which she discusses the use of equations in her reformed biology course. In one part of the interview, she expresses what sounds like an entrenched negative stance toward the role equations can play in understanding biology. However, later in the interview, when discussing a different biology topic, she takes a more positive stance toward the value of equations. These results highlight how a given student can have diverse ways of thinking about the value of bringing physics and math into biology. By highlighting how attitudes can shift in response to different tasks, instructional environments, and contextual cues, we emphasize the need to attend to these factors, rather than treating students' beliefs as fixed and stable.

A Checklist for Successful Quantitative Live Cell Imaging in Systems Biology

Science.gov (United States)

Sung, Myong-Hee

2013-01-01

Mathematical modeling of signaling and gene regulatory networks has provided unique insights about systems behaviors for many cell biological problems of medical importance. Quantitative single cell monitoring has a crucial role in advancing systems modeling of molecular networks. However, due to the multidisciplinary techniques that are necessary for adaptation of such systems biology approaches, dissemination to a wide research community has been relatively slow. In this essay, I focus on some technical aspects that are often under-appreciated, yet critical in harnessing live cell imaging methods to achieve single-cell-level understanding and quantitative modeling of molecular networks. The importance of these technical considerations will be elaborated with examples of successes and shortcomings. Future efforts will benefit by avoiding some pitfalls and by utilizing the lessons collectively learned from recent applications of imaging in systems biology. PMID:24709701

Understanding Global Change (UGC) as a Unifying Conceptual Framework for Teaching Ecology: Using UGC in a High School Biology Program to Integrate Earth Science and Biology, and to Demonstrate the Value of Modeling Global Systems in Promoting Conceptual Learning

Science.gov (United States)

Levine, J.; Bean, J. R.

2017-12-01

Global change science is ideal for NGSS-informed teaching, but presents a serious challenge to K-12 educators because it is complex and interdisciplinary- combining earth science, biology, chemistry, and physics. Global systems are themselves complex. Adding anthropogenic influences on those systems creates a formidable list of topics - greenhouse effect, climate change, nitrogen enrichment, introduced species, land-use change among them - which are often presented as a disconnected "laundry list" of "facts." This complexity, combined with public and mass-media scientific illiteracy, leaves global change science vulnerable to misrepresentation and politicization, creating additional challenges to teachers in public schools. Ample stand-alone, one-off, online resources, many of them excellent, are (to date) underutilized by teachers in the high school science course taken by most students: biology. The Understanding Global Change project (UGC) from the UC Berkeley Museum of Paleontology has created a conceptual framework that organizes, connects, and explains global systems, human and non-human drivers of change in those systems, and measurable changes in those systems. This organization and framework employ core ideas, crosscutting concepts, structure/function relationships, and system models in a unique format that facilitates authentic understanding, rather than memorization. This system serves as an organizing framework for the entire ecology unit of a forthcoming mainstream high school biology program. The UGC system model is introduced up front with its core informational graphic. The model is elaborated, step by step, by adding concepts and processes as they are introduced and explained in each chapter. The informational graphic is thus used in several ways: to organize material as it is presented, to summarize topics in each chapter and put them in perspective, and for review and critical thinking exercises that supplement the usual end-of-chapter lists of

Systems Biology of Meridians, Acupoints, and Chinese Herbs in Disease

Directory of Open Access Journals (Sweden)

Li-Ling Lin

2012-01-01

Full Text Available Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM. They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.

Informing biological design by integration of systems and synthetic biology.

Science.gov (United States)

Smolke, Christina D; Silver, Pamela A

2011-03-18

Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

Continuum analysis of biological systems conserved quantities, fluxes and forces

CERN Document Server

Suraishkumar, G K

2014-01-01

This book addresses the analysis, in the continuum regime, of biological systems at various scales, from the cellular level to the industrial one. It presents both fundamental conservation principles (mass, charge, momentum and energy) and relevant fluxes resulting from appropriate driving forces, which are important for the analysis, design and operation of biological systems. It includes the concept of charge conservation, an important principle for biological systems that is not explicitly covered in any other book of this kind. The book is organized in five parts: mass conservation; charge conservation; momentum conservation; energy conservation; and multiple conservations simultaneously applied. All mathematical aspects are presented step by step, allowing any reader with a basic mathematical background (calculus, differential equations, linear algebra, etc.) to follow the text with ease. The book promotes an intuitive understanding of all the relevant principles and in so doing facilitates their applica...

Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

Science.gov (United States)

Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

2013-01-01

Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

'Integrative Physiology 2.0': Integration of systems biology into physiology and its application to cardiovascular homeostasis

NARCIS (Netherlands)

D.W.D. Kuster (Diederik); D. Merkus (Daphne); J. van der Velden (Jolanda); A.J.M. Verhoeven (Adrie); D.J.G.M. Duncker (Dirk)

2011-01-01

textabstractSince the completion of the Human Genome Project and the advent of the large scaled unbiased '-omics' techniques, the field of systems biology has emerged. Systems biology aims to move away from the traditional reductionist molecular approach, which focused on understanding the role of

Designing and testing a classroom curriculum to teach preschoolers about the biology of physical activity: The respiration system as an underlying biological causal mechanism

Science.gov (United States)

Ewing, Tracy S.

The present study examined young children's understanding of respiration and oxygen as a source of vital energy underlying physical activity. Specifically, the purpose of the study was to explore whether a coherent biological theory, characterized by an understanding that bodily parts (heart and lungs) and processes (oxygen in respiration) as part of a biological system, can be taught as a foundational concept to reason about physical activity. The effects of a biology-based intervention curriculum designed to teach preschool children about bodily functions as a part of the respiratory system, the role of oxygen as a vital substance and how physical activity acts an energy source were examined. Participants were recruited from three private preschool classrooms (two treatment; 1 control) in Southern California and included a total of 48 four-year-old children (30 treatment; 18 control). Findings from this study suggested that young children could be taught relevant biological concepts about the role of oxygen in respiratory processes. Children who received biology-based intervention curriculum made significant gains in their understanding of the biology of respiration, identification of physical and sedentary activities. In addition these children demonstrated that coherence of conceptual knowledge was correlated with improved accuracy at activity identification and reasoning about the inner workings of the body contributing to endurance. Findings from this study provided evidence to support the benefits of providing age appropriate but complex coherent biological instruction to children in early childhood settings.

Integrating phosphoproteomics in systems biology

Directory of Open Access Journals (Sweden)

Yu Liu

2014-07-01

Full Text Available Phosphorylation of serine, threonine and tyrosine plays significant roles in cellular signal transduction and in modifying multiple protein functions. Phosphoproteins are coordinated and regulated by a network of kinases, phosphatases and phospho-binding proteins, which modify the phosphorylation states, recognize unique phosphopeptides, or target proteins for degradation. Detailed and complete information on the structure and dynamics of these networks is required to better understand fundamental mechanisms of cellular processes and diseases. High-throughput technologies have been developed to investigate phosphoproteomes in model organisms and human diseases. Among them, mass spectrometry (MS-based technologies are the major platforms and have been widely applied, which has led to explosive growth of phosphoproteomic data in recent years. New bioinformatics tools are needed to analyze and make sense of these data. Moreover, most research has focused on individual phosphoproteins and kinases. To gain a more complete knowledge of cellular processes, systems biology approaches, including pathways and networks modeling, have to be applied to integrate all components of the phosphorylation machinery, including kinases, phosphatases, their substrates, and phospho-binding proteins. This review presents the latest developments of bioinformatics methods and attempts to apply systems biology to analyze phosphoproteomics data generated by MS-based technologies. Challenges and future directions in this field will be also discussed.

Systems biology of fungal infection

Directory of Open Access Journals (Sweden)

Fabian eHorn

2012-04-01

Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

Ion beam induced fluorescence imaging in biological systems

International Nuclear Information System (INIS)

Bettiol, Andrew A.; Mi, Zhaohong; Vanga, Sudheer Kumar; Chen, Ce-belle; Tao, Ye; Watt, Frank

2015-01-01

Imaging fluorescence generated by MeV ions in biological systems such as cells and tissue sections requires a high resolution beam (<100 nm), a sensitive detection system and a fluorescent probe that has a high quantum efficiency and low bleaching rate. For cutting edge applications in bioimaging, the fluorescence imaging technique needs to break the optical diffraction limit allowing for sub-cellular structure to be visualized, leading to a better understanding of cellular function. In a nuclear microprobe this resolution requirement can be readily achieved utilizing low beam current techniques such as Scanning Transmission Ion Microscopy (STIM). In recent times, we have been able to extend this capability to fluorescence imaging through the development of a new high efficiency fluorescence detection system, and through the use of new novel fluorescent probes that are resistant to ion beam damage (bleaching). In this paper we demonstrate ion beam induced fluorescence imaging in several biological samples, highlighting the advantages and challenges associated with using this technique

Complex biological and bio-inspired systems

Energy Technology Data Exchange (ETDEWEB)

Ecke, Robert E [Los Alamos National Laboratory

2009-01-01

The understanding and characterization ofthe fundamental processes of the function of biological systems underpins many of the important challenges facing American society, from the pathology of infectious disease and the efficacy ofvaccines, to the development of materials that mimic biological functionality and deliver exceptional and novel structural and dynamic properties. These problems are fundamentally complex, involving many interacting components and poorly understood bio-chemical kinetics. We use the basic science of statistical physics, kinetic theory, cellular bio-chemistry, soft-matter physics, and information science to develop cell level models and explore the use ofbiomimetic materials. This project seeks to determine how cell level processes, such as response to mechanical stresses, chemical constituents and related gradients, and other cell signaling mechanisms, integrate and combine to create a functioning organism. The research focuses on the basic physical processes that take place at different levels ofthe biological organism: the basic role of molecular and chemical interactions are investigated, the dynamics of the DNA-molecule and its phylogenetic role are examined and the regulatory networks of complex biochemical processes are modeled. These efforts may lead to early warning algorithms ofpathogen outbreaks, new bio-sensors to detect hazards from pathomic viruses to chemical contaminants. Other potential applications include the development of efficient bio-fuel alternative-energy processes and the exploration ofnovel materials for energy usages. Finally, we use the notion of 'coarse-graining,' which is a method for averaging over less important degrees of freedom to develop computational models to predict cell function and systems-level response to disease, chemical stress, or biological pathomic agents. This project supports Energy Security, Threat Reduction, and the missions of the DOE Office of Science through its efforts to

Excited states in biological systems

International Nuclear Information System (INIS)

Cilento, G.; Zinner, K.; Bechara, E.J.H.; Duran, N.; Baptista, R.C. de; Shimizu, Y.; Augusto, O.; Faljoni-Alario, A.; Vidigal, C.C.C.; Oliveira, O.M.M.F.; Haun, M.

1979-01-01

Some aspects of bioluminescence related to bioenergetics are discussed: 1. chemical generation of excited species, by means of two general processes: electron transference and cyclic - and linear peroxide cleavage; 2. biological systems capable of generating excited states and 3. biological functions of these states, specially the non-emissive ones (tripletes). The production and the role of non-emissive excited states in biological systems are analysed, the main purpose of the study being the search for non-emissive states. Experiences carried out in biological systems are described; results and conclusions are given. (M.A.) [pt

Network Reconstruction of Dynamic Biological Systems

OpenAIRE

Asadi, Behrang

2013-01-01

Inference of network topology from experimental data is a central endeavor in biology, since knowledge of the underlying signaling mechanisms a requirement for understanding biological phenomena. As one of the most important tools in bioinformatics area, development of methods to reconstruct biological networks has attracted remarkable attention in the current decade. Integration of different data types can lead to remarkable improvements in our ability to identify the connectivity of differe...

Quantum mechanical simulation methods for studying biological systems

International Nuclear Information System (INIS)

Bicout, D.; Field, M.

1996-01-01

Most known biological mechanisms can be explained using fundamental laws of physics and chemistry and a full understanding of biological processes requires a multidisciplinary approach in which all the tools of biology, chemistry and physics are employed. An area of research becoming increasingly important is the theoretical study of biological macromolecules where numerical experimentation plays a double role of establishing a link between theoretical models and predictions and allowing a quantitative comparison between experiments and models. This workshop brought researchers working on different aspects of the development and application of quantum mechanical simulation together, assessed the state-of-the-art in the field and highlighted directions for future research. Fourteen lectures (theoretical courses and specialized seminars) deal with following themes: 1) quantum mechanical calculations of large systems, 2) ab initio molecular dynamics where the calculation of the wavefunction and hence the energy and forces on the atoms for a system at a single nuclear configuration are combined with classical molecular dynamics algorithms in order to perform simulations which use a quantum mechanical potential energy surface, 3) quantum dynamical simulations, electron and proton transfer processes in proteins and in solutions and finally, 4) free seminars that helped to enlarge the scope of the workshop. (N.T.)

Telemetry System of Biological Parameters

Directory of Open Access Journals (Sweden)

Jan Spisak

2005-01-01

Full Text Available The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consumption, weight and maximal device mobility. This system has to eliminate signal noise, which is created by biological artifacts and disturbances during the data transfer.

Logical analysis of biological systems

DEFF Research Database (Denmark)

Mardare, Radu Iulian

2005-01-01

R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

Energy Technology Data Exchange (ETDEWEB)

Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

2011-02-01

The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

Institute for Genomics and Systems Biology

Science.gov (United States)

Institute for Genomics and Systems Biology Discover. Predict. Improve. Advancing Human and , 2015 See all Research Papers Featured Video Introduction to Systems Biology Video: Introduction to Systems Biology News Jack Gilbert Heading UChicago Startup that Aims to Predict Behavior of Trillions of

Systems biology of lactic acid bacteria: a critical review.

Science.gov (United States)

Teusink, Bas; Bachmann, Herwig; Molenaar, Douwe

2011-08-30

Understanding the properties of a system as emerging from the interaction of well described parts is the most important goal of Systems Biology. Although in the practice of Lactic Acid Bacteria (LAB) physiology we most often think of the parts as the proteins and metabolites, a wider interpretation of what a part is can be useful. For example, different strains or species can be the parts of a community, or we could study only the chemical reactions as the parts of metabolism (and forgetting about the enzymes that catalyze them), as is done in flux balance analysis. As long as we have some understanding of the properties of these parts, we can investigate whether their interaction leads to novel or unanticipated behaviour of the system that they constitute. There has been a tendency in the Systems Biology community to think that the collection and integration of data should continue ad infinitum, or that we will otherwise not be able to understand the systems that we study in their details. However, it may sometimes be useful to take a step back and consider whether the knowledge that we already have may not explain the system behaviour that we find so intriguing. Reasoning about systems can be difficult, and may require the application of mathematical techniques. The reward is sometimes the realization of unexpected conclusions, or in the worst case, that we still do not know enough details of the parts, or of the interactions between them. We will discuss a number of cases, with a focus on LAB-related work, where a typical systems approach has brought new knowledge or perspective, often counterintuitive, and clashing with conclusions from simpler approaches. Also novel types of testable hypotheses may be generated by the systems approach, which we will illustrate. Finally we will give an outlook on the fields of research where the systems approach may point the way for the near future.

Shape understanding system machine understanding and human understanding

CERN Document Server

Les, Zbigniew

2015-01-01

This is the third book presenting selected results of research on the further development of the shape understanding system (SUS) carried out by authors in the newly founded Queen Jadwiga Research Institute of Understanding. In this book the new term Machine Understanding is introduced referring to a new area of research aiming to investigate the possibility of building machines with the ability to understand. It is presented that SUS needs to some extent mimic human understanding and for this reason machines are evaluated according to the rules applied for the evaluation of human understanding. The book shows how to formulate problems and how it can be tested if the machine is able to solve these problems.    

Biophysics and systems biology.

Science.gov (United States)

Noble, Denis

2010-03-13

Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights.

Inorganic concepts relevant to metal binding, activity, and toxicity in a biological system

Energy Technology Data Exchange (ETDEWEB)

Hoeschele, J.D. (Warner-Lambert Co., Ann Arbor, MI (USA). Parke-Davis Pharmaceutical Research Div.); Turner, J.E.; England, M.W. (Oak Ridge National Lab., TN (USA))

1990-01-01

The purpose of this paper is to review selected physical and inorganic concepts and factors which might be important in assessing and/or understanding the fact and disposition of a metal system in a biological environment. Hopefully, such inquiries will ultimately permit us to understand, rationalize, and predict differences and trends in biological effects as a function of the basic nature of a metal system and, in optimal cases, serve as input to a system of guidelines for the notion of Chemical Dosimetry.'' The plan of this paper is to first review, in general terms, the basic principles of the Crystal Field Theory (CFT), a unifying theory of bonding in metal complexes. This will provide the necessary theoretical background for the subsequent discussion of selected concepts and factors. 21 refs., 7 figs., 6 tabs.

The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

Science.gov (United States)

Ganguli, Suman; Hunt, C Anthony

2004-01-01

Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

Compartmental study of biological systems

International Nuclear Information System (INIS)

Moretti, J.L.

1975-01-01

The compartmental analysis of biological system is dealt with on several chapters devoted successively to: terminology; a mathematical and symbolic account of a system at equilibrium; different compartment systems; analysis of the experimental results. For this it is pointed out that the application of compartmental systems to biological phenomena is not always without danger. Sometimes the compartmental system established in a reference subject fails to conform in the patient. The compartments can divide into two or join together, completely changing the aspect of the system so that parameters calculated with the old model become entirely false. The conclusion is that the setting up of a compartmental system to represent a biological phenomenon is a tricky undertaking and the results must be constantly criticized and questioned [fr

Philosophy of Systems and Synthetic Biology

DEFF Research Database (Denmark)

Green, Sara

2017-01-01

This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

Systemic thinking fundamentals for understanding problems and messes

CERN Document Server

Hester, Patrick T

2014-01-01

Whether you’re an academic or a practitioner, a sociologist, a manager, or an engineer, one can benefit from learning to think systemically.  Problems (and messes) are everywhere and they’re getting more complicated every day.  How we think about these problems determines whether or not we’ll be successful in understanding and addressing them.  This book presents a novel way to think about problems (and messes) necessary to attack these always-present concerns.  The approach draws from disciplines as diverse as mathematics, biology, and psychology to provide a holistic method for dealing with problems that can be applied to any discipline. This book develops the systemic thinking paradigm, and introduces practical guidelines for the deployment of a systemic thinking approach.

Growing trend of CE at the omics level: the frontier of systems biology--an update.

Science.gov (United States)

Ban, Eunmi; Park, Soo Hyun; Kang, Min-Jung; Lee, Hyun-Jung; Song, Eun Joo; Yoo, Young Sook

2012-01-01

Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

Science.gov (United States)

Williams, Tim D; Turan, Nil; Diab, Amer M; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L; Hrydziuszko, Olga; Lyons, Brett P; Stentiford, Grant D; Herbert, John M; Abraham, Joseph K; Katsiadaki, Ioanna; Leaver, Michael J; Taggart, John B; George, Stephen G; Viant, Mark R; Chipman, Kevin J; Falciani, Francesco

2011-08-01

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

Students' Energy Understanding Across Biology, Chemistry, and Physics Contexts

Science.gov (United States)

Opitz, S. T.; Neumann, K.; Bernholt, S.; Harms, U.

2017-07-01

Energy is considered both as a disciplinary core idea and as a concept cutting across science disciplines. Most previous approaches studied progressing energy understanding in specific disciplinary contexts, while disregarding the relation of understanding across them. Hence, this study provides a systematic analysis of cross-disciplinary energy learning. On the basis of a cross-sectional study with n = 742 students from grades 6, 8, and 10, we analyze students' progression in understanding energy across biology, chemistry, and physics contexts. The study is guided by three hypothetical scenarios that describe how the connection between energy understanding in the three disciplinary contexts changes across grade levels. These scenarios are compared using confirmatory factor analysis (CFA). The results suggest that, from grade 6 to grade 10, energy understanding in the three disciplinary contexts is highly interrelated, thus indicating a parallel progression of energy understanding in the three disciplinary contexts. In our study, students from grade 6 onwards appeared to have few problems to apply one energy understanding across the three disciplinary contexts. These findings were unexpected, as previous research concluded that students likely face difficulties in connecting energy learning across disciplinary boundaries. Potential reasons for these results and the characteristics of the observed cross-disciplinary energy understanding are discussed in the light of earlier findings and implications for future research, and the teaching of energy as a core idea and a crosscutting concept are addressed.

Integrating systems biology models and biomedical ontologies.

Science.gov (United States)

Hoehndorf, Robert; Dumontier, Michel; Gennari, John H; Wimalaratne, Sarala; de Bono, Bernard; Cook, Daniel L; Gkoutos, Georgios V

2011-08-11

Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

Calculating life? Duelling discourses in interdisciplinary systems biology.

Science.gov (United States)

Calvert, Jane; Fujimura, Joan H

2011-06-01

A high profile context in which physics and biology meet today is in the new field of systems biology. Systems biology is a fascinating subject for sociological investigation because the demands of interdisciplinary collaboration have brought epistemological issues and debates front and centre in discussions amongst systems biologists in conference settings, in publications, and in laboratory coffee rooms. One could argue that systems biologists are conducting their own philosophy of science. This paper explores the epistemic aspirations of the field by drawing on interviews with scientists working in systems biology, attendance at systems biology conferences and workshops, and visits to systems biology laboratories. It examines the discourses of systems biologists, looking at how they position their work in relation to previous types of biological inquiry, particularly molecular biology. For example, they raise the issue of reductionism to distinguish systems biology from molecular biology. This comparison with molecular biology leads to discussions about the goals and aspirations of systems biology, including epistemic commitments to quantification, rigor and predictability. Some systems biologists aspire to make biology more similar to physics and engineering by making living systems calculable, modelable and ultimately predictable-a research programme that is perhaps taken to its most extreme form in systems biology's sister discipline: synthetic biology. Other systems biologists, however, do not think that the standards of the physical sciences are the standards by which we should measure the achievements of systems biology, and doubt whether such standards will ever be applicable to 'dirty, unruly living systems'. This paper explores these epistemic tensions and reflects on their sociological dimensions and their consequences for future work in the life sciences. Copyright © 2010 Elsevier Ltd. All rights reserved.

Heuristic Strategies in Systems Biology

Directory of Open Access Journals (Sweden)

Fridolin Gross

2016-06-01

Full Text Available Systems biology is sometimes presented as providing a superior approach to the problem of biological complexity. Its use of ‘unbiased’ methods and formal quantitative tools might lead to the impression that the human factor is effectively eliminated. However, a closer look reveals that this impression is misguided. Systems biologists cannot simply assemble molecular information and compute biological behavior. Instead, systems biology’s main contribution is to accelerate the discovery of mechanisms by applying models as heuristic tools. These models rely on a variety of idealizing and simplifying assumptions in order to be efficient for this purpose. The strategies of systems biologists are similar to those of experimentalists in that they attempt to reduce the complexity of the discovery process. Analyzing and comparing these strategies, or ‘heuristics’, reveals the importance of the human factor in computational approaches and helps to situate systems biology within the epistemic landscape of the life sciences.

Quantum Dynamics in Biological Systems

Science.gov (United States)

Shim, Sangwoo

In the first part of this dissertation, recent efforts to understand quantum mechanical effects in biological systems are discussed. Especially, long-lived quantum coherences observed during the electronic energy transfer process in the Fenna-Matthews-Olson complex at physiological condition are studied extensively using theories of open quantum systems. In addition to the usual master equation based approaches, the effect of the protein structure is investigated in atomistic detail through the combined application of quantum chemistry and molecular dynamics simulations. To evaluate the thermalized reduced density matrix, a path-integral Monte Carlo method with a novel importance sampling approach is developed for excitons coupled to an arbitrary phonon bath at a finite temperature. In the second part of the thesis, simulations of molecular systems and applications to vibrational spectra are discussed. First, the quantum dynamics of a molecule is simulated by combining semiclassical initial value representation and density funcitonal theory with analytic derivatives. A computationally-tractable approximation to the sum-of-states formalism of Raman spectra is subsequently discussed.

Using systems and structure biology tools to dissect cellular phenotypes.

Science.gov (United States)

Floratos, Aris; Honig, Barry; Pe'er, Dana; Califano, Andrea

2012-01-01

The Center for the Multiscale Analysis of Genetic Networks (MAGNet, http://magnet.c2b2.columbia.edu) was established in 2005, with the mission of providing the biomedical research community with Structural and Systems Biology algorithms and software tools for the dissection of molecular interactions and for the interaction-based elucidation of cellular phenotypes. Over the last 7 years, MAGNet investigators have developed many novel analysis methodologies, which have led to important biological discoveries, including understanding the role of the DNA shape in protein-DNA binding specificity and the discovery of genes causally related to the presentation of malignant phenotypes, including lymphoma, glioma, and melanoma. Software tools implementing these methodologies have been broadly adopted by the research community and are made freely available through geWorkbench, the Center's integrated analysis platform. Additionally, MAGNet has been instrumental in organizing and developing key conferences and meetings focused on the emerging field of systems biology and regulatory genomics, with special focus on cancer-related research.

Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

DEFF Research Database (Denmark)

Thøgersen, Juliane Charlotte

modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....... and metabolic pathways that are necessary or related to establishment of chronic infections. Archetypal analysis showed to be successful in extracting relevant phenotypes from global gene expression da-­‐ ta. Furthermore, genome-­‐scale metabolic modeling showed to be useful in connecting the genotype...

Is synthetic biology mechanical biology?

Science.gov (United States)

Holm, Sune

2015-12-01

A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

Collaborative Systems Biology Projects for the Military Medical Community.

Science.gov (United States)

Zalatoris, Jeffrey J; Scheerer, Julia B; Lebeda, Frank J

2017-09-01

This pilot study was conducted to examine, for the first time, the ongoing systems biology research and development projects within the laboratories and centers of the U.S. Army Medical Research and Materiel Command (USAMRMC). The analysis has provided an understanding of the breadth of systems biology activities, resources, and collaborations across all USAMRMC subordinate laboratories. The Systems Biology Collaboration Center at USAMRMC issued a survey regarding systems biology research projects to the eight U.S.-based USAMRMC laboratories and centers in August 2016. This survey included a data call worksheet to gather self-identified project and programmatic information. The general topics focused on the investigators and their projects, on the project's research areas, on omics and other large data types being collected and stored, on the analytical or computational tools being used, and on identifying intramural (i.e., USAMRMC) and extramural collaborations. Among seven of the eight laboratories, 62 unique systems biology studies were funded and active during the final quarter of fiscal year 2016. Of 29 preselected medical Research Task Areas, 20 were associated with these studies, some of which were applicable to two or more Research Task Areas. Overall, studies were categorized among six general types of objectives: biological mechanisms of disease, risk of/susceptibility to injury or disease, innate mechanisms of healing, diagnostic and prognostic biomarkers, and host/patient responses to vaccines, and therapeutic strategies including host responses to therapies. We identified eight types of omics studies and four types of study subjects. Studies were categorized on a scale of increasing complexity from single study subject/single omics technology studies (23/62) to studies integrating results across two study subject types and two or more omics technologies (13/62). Investigators at seven USAMRMC laboratories had collaborations with systems biology experts

Applicability of Computational Systems Biology in Toxicology

DEFF Research Database (Denmark)

Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure

2014-01-01

be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

Science.gov (United States)

De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

2010-03-01

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

Do Zoo Visitors Need Zoology Knowledge to Understand Conservation Messages? An Exploration of the Public Understanding of Animal Biology and of the Conservation of Biodiversity in a Zoo Setting

Science.gov (United States)

Dove, Tracy; Byrne, Jenny

2014-01-01

This study explores the current knowledge and understanding about animal biology of zoo visitors and investigates whether knowledge of animal biology influences the ability of people to understand how human activity affects biodiversity. Zoos can play a role in the development of scientific literacy in the fields of animal biology and biodiversity…

Application of integrative genomics and systems biology to conventional and in vitro reproductive traits in cattle

DEFF Research Database (Denmark)

Mazzoni, Gianluca; Pedersen, Hanne S.; de Oliveira Junior, Gerson A.

2017-01-01

by both conventional and ARTs such as OPU-IVP. The integration of systems biology information across different biological layers generates a complete view of the different molecular networks that control complex traits and can provide a strong contribution to the understanding of traits related to ARTs....

Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

Science.gov (United States)

Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

2016-02-01

The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

Iterative Systems Biology for Medicine – time for advancing from network signature to mechanistic equations

KAUST Repository

Gomez-Cabrero, David

2017-05-09

The rise and growth of Systems Biology following the sequencing of the human genome has been astounding. Early on, an iterative wet-dry methodology was formulated which turned out as a successful approach in deciphering biological complexity. Such type of analysis effectively identified and associated molecular network signatures operative in biological processes across different systems. Yet, it has proven difficult to distinguish between causes and consequences, thus making it challenging to attack medical questions where we require precise causative drug targets and disease mechanisms beyond a web of associated markers. Here we review principal advances with regard to identification of structure, dynamics, control, and design of biological systems, following the structure in the visionary review from 2002 by Dr. Kitano. Yet, here we find that the underlying challenge of finding the governing mechanistic system equations enabling precision medicine remains open thus rendering clinical translation of systems biology arduous. However, stunning advances in raw computational power, generation of high-precision multi-faceted biological data, combined with powerful algorithms hold promise to set the stage for data-driven identification of equations implicating a fundamental understanding of living systems during health and disease.

Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

Directory of Open Access Journals (Sweden)

Tim D Williams

2011-08-01

Full Text Available The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

Evaluation of impedance on biological Tissues using automatic control measurement system

Energy Technology Data Exchange (ETDEWEB)

Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo [Pusan National University, Yangsan (Korea, Republic of); Lee, Moo Seok; Kim, Sang Sik [Pusan National University, Busan (Korea, Republic of); Kim, Gun FDo; Lee, Jong Kyu [Pukyung National University, Busan (Korea, Republic of)

2015-08-15

Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

Evaluation of impedance on biological Tissues using automatic control measurement system

International Nuclear Information System (INIS)

Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo; Lee, Moo Seok; Kim, Sang Sik; Kim, Gun FDo; Lee, Jong Kyu

2015-01-01

Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

Science.gov (United States)

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

2010-02-01

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell

Understanding the biological responses of nanostructured metals and surfaces

Science.gov (United States)

Lowe, Terry C.; Reiss, Rebecca A.

2014-08-01

Metals produced by Severe Plastic Deformation (SPD) offer distinct advantages for medical applications such as orthopedic devices, in part because of their nanostructured surfaces. We examine the current theoretical foundations and state of knowledge for nanostructured biomaterials surface optimization within the contexts that apply to bulk nanostructured metals, differentiating how their microstructures impact osteogenesis, in particular, for Ultrafine Grained (UFG) titanium. Then we identify key gaps in the research to date, pointing out areas which merit additional focus within the scientific community. For example, we highlight the potential of next-generation DNA sequencing techniques (NGS) to reveal gene and non-coding RNA (ncRNA) expression changes induced by nanostructured metals. While our understanding of bio-nano interactions is in its infancy, nanostructured metals are already being marketed or developed for medical devices such as dental implants, spinal devices, and coronary stents. Our ability to characterize and optimize the biological response of cells to SPD metals will have synergistic effects on advances in materials, biological, and medical science.

Understanding the biological responses of nanostructured metals and surfaces

International Nuclear Information System (INIS)

Lowe, Terry C; A Reiss, Rebecca

2014-01-01

Metals produced by Severe Plastic Deformation (SPD) offer distinct advantages for medical applications such as orthopedic devices, in part because of their nanostructured surfaces. We examine the current theoretical foundations and state of knowledge for nanostructured biomaterials surface optimization within the contexts that apply to bulk nanostructured metals, differentiating how their microstructures impact osteogenesis, in particular, for Ultrafine Grained (UFG) titanium. Then we identify key gaps in the research to date, pointing out areas which merit additional focus within the scientific community. For example, we highlight the potential of next-generation DNA sequencing techniques (NGS) to reveal gene and non-coding RNA (ncRNA) expression changes induced by nanostructured metals. While our understanding of bio-nano interactions is in its infancy, nanostructured metals are already being marketed or developed for medical devices such as dental implants, spinal devices, and coronary stents. Our ability to characterize and optimize the biological response of cells to SPD metals will have synergistic effects on advances in materials, biological, and medical science

Multiway modeling and analysis in stem cell systems biology

Directory of Open Access Journals (Sweden)

Vandenberg Scott L

2008-07-01

Full Text Available Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.. A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells. Results We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a

Perceptual Influence of Ugandan Biology Students' Understanding of HIV/AIDS

Science.gov (United States)

Mutonyi, Harriet; Nashon, Samson; Nielsen, Wendy S.

2010-08-01

In Uganda, curbing the spread of HIV/AIDS has largely depended on public and private media messages about the disease. Media campaigns based on Uganda’s cultural norms of communication are metaphorical, analogical and simile-like. The topic of HIV/AIDS has been introduced into the Senior Three (Grade 11) biology curriculum in Uganda. To what extent do students’ pre-conceptions of the disease, based on these media messages influence students’ development of conceptual understanding of the disease, its transmission and prevention? Of significant importance is the impact the conceptions students have developed from the indirect media messages on classroom instruction on HIV/AIDS. The study is based in a theoretical framework of conceptual change in science learning. An interpretive case study to determine the impact of Ugandan students’ conceptions or perceptions on classroom instruction about HIV/AIDS, involving 160 students aged 15-17, was conducted in four different Ugandan high schools: girls boarding, boys boarding, mixed boarding, and mixed day. Using questionnaires, focus group discussions, recorded biology lessons and informal interviews, students’ preconceptions of HIV/AIDS and how these impact lessons on HIV/AIDS were discerned. These preconceptions fall into four main categories: religious, political, conspiracy and traditional African worldviews. Results of data analysis suggest that students’ prior knowledge is persistent even after biology instructions. This has implications for current teaching approaches, which are mostly teacher-centred in Ugandan schools. A rethinking of the curriculum with the intent of offering science education programs that promote understanding of the science of HIV/AIDS as opposed to what is happening now—insensitivity to misconceptions about the disease—is needed.

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

Science.gov (United States)

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

understanding of biological effects of nanoparticles on the reproductive system.

A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

Science.gov (United States)

Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

2016-06-17

Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

Conceptions of Memorizing and Understanding in Learning, and Self-Efficacy Held by University Biology Majors

Science.gov (United States)

Lin, Tzu-Chiang; Liang, Jyh-Chong; Tsai, Chin-Chung

2015-01-01

This study aims to explore Taiwanese university students' conceptions of learning biology as memorizing or as understanding, and their self-efficacy. To this end, two questionnaires were utilized to survey 293 Taiwanese university students with biology-related majors. A questionnaire for measuring students' conceptions of memorizing and…

Dynamic systems for everyone understanding how our world works

CERN Document Server

Ghosh, Asish

2017-01-01

Systems are everywhere and we are surrounded by them. We are a complex amalgam of systems that enable us to interact with an endless array of external systems in our daily lives. They are electrical, mechanical, social, biological, and many other types that control our environment and our well-being. By appreciating how these systems function, will broaden our understanding of how our world works. Readers from a variety of disciplines will benefit from the knowledge of system behavior they will gain from this book and will be able to apply those principles in various contexts. The treatment of the subject is non-mathematical, and the book considers some of the latest concepts in the systems discipline, such as agent based systems, optimization, and discrete events and procedures. The diverse range of examples provided in this book, will allow readers to: Apply system knowledge at work and in daily life without deep mathematical knowledge; Build models and simulate system behaviors on a personal computer; Opti...

Genomes, Phylogeny, and Evolutionary Systems Biology

Energy Technology Data Exchange (ETDEWEB)

Medina, Monica

2005-03-25

With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

Comparative systems biology between human and animal models based on next-generation sequencing methods.

Science.gov (United States)

Zhao, Yu-Qi; Li, Gong-Hua; Huang, Jing-Fei

2013-04-01

Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

Building biological foundries for next-generation synthetic biology.

Science.gov (United States)

Chao, Ran; Yuan, YongBo; Zhao, HuiMin

2015-07-01

Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

Aspergilli: Systems biology and industrial applications

DEFF Research Database (Denmark)

Knuf, Christoph; Nielsen, Jens

2012-01-01

possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....

Microgravity Fluids for Biology, Workshop

Science.gov (United States)

Griffin, DeVon; Kohl, Fred; Massa, Gioia D.; Motil, Brian; Parsons-Wingerter, Patricia; Quincy, Charles; Sato, Kevin; Singh, Bhim; Smith, Jeffrey D.; Wheeler, Raymond M.

2013-01-01

Microgravity Fluids for Biology represents an intersection of biology and fluid physics that present exciting research challenges to the Space Life and Physical Sciences Division. Solving and managing the transport processes and fluid mechanics in physiological and biological systems and processes are essential for future space exploration and colonization of space by humans. Adequate understanding of the underlying fluid physics and transport mechanisms will provide new, necessary insights and technologies for analyzing and designing biological systems critical to NASAs mission. To enable this mission, the fluid physics discipline needs to work to enhance the understanding of the influence of gravity on the scales and types of fluids (i.e., non-Newtonian) important to biology and life sciences. In turn, biomimetic, bio-inspired and synthetic biology applications based on physiology and biology can enrich the fluid mechanics and transport phenomena capabilities of the microgravity fluid physics community.

Model checking biological systems described using ambient calculus

DEFF Research Database (Denmark)

Mardare, Radu Iulian; Priami, Corrado; Qualia, Paola

2005-01-01

Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005.......Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005....

Complexity, Analysis and Control of Singular Biological Systems

CERN Document Server

Zhang, Qingling; Zhang, Xue

2012-01-01

Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

Graphics processing units in bioinformatics, computational biology and systems biology.

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Nobile, Marco S; Cazzaniga, Paolo; Tangherloni, Andrea; Besozzi, Daniela

2017-09-01

Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU-powered tools here reviewed is available at http://bit.ly/gputools. © The Author 2016. Published by Oxford University Press.

Systems biology of human metabolism - Defining the epithelial to mesenchymal transition and the activity of human gluconokinase

OpenAIRE

Rohatgi, Neha

2016-01-01

Studying human metabolism is crucial for the understanding of diseases and improvement of therapy as metabolic alterations are central to a number of human diseases. A variety of experimental disciplines, such as biochemistry, biophysics and systems biology are involved in the elucidation of metabolic pathways. The work presented in this thesis is divided into three main studies, which expand the knowledge of human metabolism using systems biology and biochemical techniques....

A system for success: BMC Systems Biology, a new open access journal.

Science.gov (United States)

Hodgkinson, Matt J; Webb, Penelope A

2007-09-04

BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

Hierarchical structure of biological systems: a bioengineering approach.

Science.gov (United States)

Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M

2014-01-01

A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems.

A second inheritance system: the extension of biology through culture.

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Whiten, Andrew

2017-10-06

By the mid-twentieth century (thus following the 'Modern Synthesis' in evolutionary biology), the behavioural sciences offered only the sketchy beginnings of a scientific literature documenting evidence for cultural inheritance in animals-the transmission of traditional behaviours via learning from others (social learning). By contrast, recent decades have seen a massive growth in the documentation of such cultural phenomena, driven by long-term field studies and complementary laboratory experiments. Here, I review the burgeoning scope of discoveries in this field, which increasingly suggest that this 'second inheritance system', built on the shoulders of the primary genetic inheritance system, occurs widely among vertebrates and possibly in invertebrates too. Its novel characteristics suggest significant implications for our understanding of evolutionary biology. I assess the extent to which this second system extends the scope of evolution, both by echoing principal properties of the primary, organic evolutionary system, and going beyond it in significant ways. This is well established in human cultural evolution; here, I address animal cultures more generally. The further major, and related, question concerns the extent to which the consequences of widespread animal cultural transmission interact with the primary, genetically based inheritance systems, shaping organic evolution.

Review of Biological Network Data and Its Applications

Directory of Open Access Journals (Sweden)

Donghyeon Yu

2013-12-01

Full Text Available Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

An engineering design approach to systems biology.

Science.gov (United States)

Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

2017-07-17

Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

The Feasibility of Systems Thinking in Biology Education

Science.gov (United States)

Boersma, Kerst; Waarlo, Arend Jan; Klaassen, Kees

2011-01-01

Systems thinking in biology education is an up and coming research topic, as yet with contrasting feasibility claims. In biology education systems thinking can be understood as thinking backward and forward between concrete biological objects and processes and systems models representing systems theoretical characteristics. Some studies claim that…

The common extremalities in biology and physics maximum energy dissipation principle in chemistry, biology, physics and evolution

CERN Document Server

Moroz, Adam

2011-01-01

This book is the first unified systemic description of dissipative phenomena, taking place in biology, and non-dissipative (conservative) phenomena, which is more relevant to physics. Fully updated and revised, this new edition extends our understanding of nonlinear phenomena in biology and physics from the extreme / optimal perspective. The first book to provide understanding of physical phenomena from a biological perspective and biological phenomena from a physical perspective Discusses emerging fields and analysis Provides examples.

Redox and Ionic Homeostasis Regulations against Oxidative, Salinity and Drought Stress in Wheat (A Systems Biology Approach

Directory of Open Access Journals (Sweden)

Zahid Hussain Shah

2017-10-01

Full Text Available Systems biology and omics has provided a comprehensive understanding about the dynamics of the genome, metabolome, transcriptome, and proteome under stress. In wheat, abiotic stresses trigger specific networks of pathways involved in redox and ionic homeostasis as well as osmotic balance. These networks are considerably more complicated than those in model plants, and therefore, counter models are proposed by unifying the approaches of omics and stress systems biology. Furthermore, crosstalk among these pathways is monitored by the regulation and streaming of transcripts and genes. In this review, we discuss systems biology and omics as a promising tool to study responses to oxidative, salinity, and drought stress in wheat.

Answering biological questions: Querying a systems biology database for nutrigenomics

NARCIS (Netherlands)

Evelo, C.T.; Bochove, K. van; Saito, J.T.

2011-01-01

The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A

Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems

Science.gov (United States)

2011-01-01

Background We review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively. Results We describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equation f = f (f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing. Conclusions We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete. PMID:21689427

Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

Science.gov (United States)

Jalili, Mahdi

2018-03-01

I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

A systems biology approach to study systemic inflammation.

Science.gov (United States)

Chen, Bor-Sen; Wu, Chia-Chou

2014-01-01

Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

Understanding and Enhancing Soil Biological Health: The Solution for Reversing Soil Degradation

Directory of Open Access Journals (Sweden)

R. Michael Lehman

2015-01-01

Full Text Available Our objective is to provide an optimistic strategy for reversing soil degradation by increasing public and private research efforts to understand the role of soil biology, particularly microbiology, on the health of our world’s soils. We begin by defining soil quality/soil health (which we consider to be interchangeable terms, characterizing healthy soil resources, and relating the significance of soil health to agroecosystems and their functions. We examine how soil biology influences soil health and how biological properties and processes contribute to sustainability of agriculture and ecosystem services. We continue by examining what can be done to manipulate soil biology to: (i increase nutrient availability for production of high yielding, high quality crops; (ii protect crops from pests, pathogens, weeds; and (iii manage other factors limiting production, provision of ecosystem services, and resilience to stresses like droughts. Next we look to the future by asking what needs to be known about soil biology that is not currently recognized or fully understood and how these needs could be addressed using emerging research tools. We conclude, based on our perceptions of how new knowledge regarding soil biology will help make agriculture more sustainable and productive, by recommending research emphases that should receive first priority through enhanced public and private research in order to reverse the trajectory toward global soil degradation.

Surface mixing and biological activity in the four Eastern Boundary Upwelling Systems

Directory of Open Access Journals (Sweden)

V. Rossi

2009-08-01

Full Text Available Eastern Boundary Upwelling Systems (EBUS are characterized by a high productivity of plankton associated with large commercial fisheries, thus playing key biological and socio-economical roles. Since they are populated by several physical oceanic structures such as filaments and eddies, which interact with the biological processes, it is a major challenge to study this sub- and mesoscale activity in connection with the chlorophyll distribution. The aim of this work is to make a comparative study of these four upwelling systems focussing on their surface stirring, using the Finite Size Lyapunov Exponents (FSLEs, and their biological activity, based on satellite data. First, the spatial distribution of horizontal mixing is analysed from time averages and from probability density functions of FSLEs, which allow us to divide each areas in two different subsystems. Then we studied the temporal variability of surface stirring focussing on the annual and seasonal cycle. We also proposed a ranking of the four EBUS based on the averaged mixing intensity. When investigating the links with chlorophyll concentration, the previous subsystems reveal distinct biological signatures. There is a global negative correlation between surface horizontal mixing and chlorophyll standing stocks over the four areas. To try to better understand this inverse relationship, we consider the vertical dimension by looking at the Ekman-transport and vertical velocities. We suggest the possibility of a changing response of the phytoplankton to sub/mesoscale turbulence, from a negative effect in the very productive coastal areas to a positive one in the open ocean. This study provides new insights for the understanding of the variable biological productivity in the ocean, which results from both dynamics of the marine ecosystem and of the 3-D turbulent medium.

Two sides of the same coin? The (techno)epistemic cultures of systems and synthetic biology.

Science.gov (United States)

Kastenhofer, Karen

2013-06-01

Systems and synthetic biology both emerged around the turn of this century as labels for new research approaches. Although their disciplinary status as well as their relation to each other is rarely discussed in depth, now and again the idea is invoked that both approaches represent 'two sides of the same coin'. The following paper focuses on this general notion and compares it with empirical findings concerning the epistemic cultures prevalent in the two contexts. Drawing on interviews with researchers from both fields, on participatory observation in conferences and courses and on documentary analysis, this paper delineates differences and similarities, incompatibilities and blurred boundaries. By reconstructing systems and synthetic biology's epistemic cultures, this paper argues that they represent two 'communities of vision', encompassing heterogeneous practices. Understanding the relation of the respective visions of understanding nature and engineering life is seen as indispensible for the characterisation of (techno)science in more general terms. Depending on the conceptualisation of understanding and construction (or: science and engineering), related practices such as in silico modelling for enhancing understanding or enabling engineering can either be seen as incommensurable or 'two sides of one coin'. Copyright © 2013 Elsevier Ltd. All rights reserved.

‘Integrative Physiology 2.0’: integration of systems biology into physiology and its application to cardiovascular homeostasis

Science.gov (United States)

Kuster, Diederik W D; Merkus, Daphne; van der Velden, Jolanda; Verhoeven, Adrie J M; Duncker, Dirk J

2011-01-01

Since the completion of the Human Genome Project and the advent of the large scaled unbiased ‘-omics’ techniques, the field of systems biology has emerged. Systems biology aims to move away from the traditional reductionist molecular approach, which focused on understanding the role of single genes or proteins, towards a more holistic approach by studying networks and interactions between individual components of networks. From a conceptual standpoint, systems biology elicits a ‘back to the future’ experience for any integrative physiologist. However, many of the new techniques and modalities employed by systems biologists yield tremendous potential for integrative physiologists to expand their tool arsenal to (quantitatively) study complex biological processes, such as cardiac remodelling and heart failure, in a truly holistic fashion. We therefore advocate that systems biology should not become/stay a separate discipline with ‘-omics’ as its playing field, but should be integrated into physiology to create ‘Integrative Physiology 2.0’. PMID:21224228

Physics and biology

International Nuclear Information System (INIS)

Frauenfelder, H.

1988-01-01

The author points out that the coupling between physics and biology is becoming closer as time goes on. He tries to show that physical studies on biological systems not only yield insight into biology but also provide results of interest to physics. Biological systems are extremly complex system. Ideally one would like to understand the behavior of such systems in terms of the behavior of its constituent atoms. Since in small organisms this may be 10 20 atoms, it is clear these are not simple many-body systems. He reviews the basic elements of cells and then considers the broader questions of structure, complexity, and function, which must be looked at on levels from the cell to the organism. Despite the vast amount of observational material already in existence, biophysics and biological physics are only at a beginning. We can expect that physics will continue to interact strongly with biology. Actually, the connection also includes chemistry and mathematics. New tools that become available in physics will continue to be applied to biological problems. We can expect that the flow of information will not be one way; biological systems will provide new information on many old and new parts of physics, from reaction theory and transport phenomena to complexity, cooperativity, and nonlinear processes

How sulphate-reducing microorganisms cope with stress: Lessons from systems biology

Energy Technology Data Exchange (ETDEWEB)

Zhou, J.; He, Q.; Hemme, C.L.; Mukhopadhyay, A.; Hillesland, K.; Zhou, A.; He, Z.; Nostrand, J.D. Van; Hazen, T.C.; Stahl, D.A.; Wall, J.D.; Arkin, A.P.

2011-04-01

Sulphate-reducing microorganisms (SRMs) are a phylogenetically diverse group of anaerobes encompassing distinct physiologies with a broad ecological distribution. As SRMs have important roles in the biogeochemical cycling of carbon, nitrogen, sulphur and various metals, an understanding of how these organisms respond to environmental stresses is of fundamental and practical importance. In this Review, we highlight recent applications of systems biology tools in studying the stress responses of SRMs, particularly Desulfovibrio spp., at the cell, population, community and ecosystem levels. The syntrophic lifestyle of SRMs is also discussed, with a focus on system-level analyses of adaptive mechanisms. Such information is important for understanding the microbiology of the global sulphur cycle and for developing biotechnological applications of SRMs for environmental remediation, energy production, biocorrosion control, wastewater treatment and mineral recovery.

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life

NARCIS (Netherlands)

Kaput, J.; Ommen, B. van; Kremer, S.H.A.; Priami, C.; Pontes Monteiro, J.; Morine, M.; Pepping, F.; Diaz, Z.; Fenech, M.; He, Y.; Albers, R.; Drevon, C.A.; Evelo, C.T.; Hancock, R.E.W.; IJsselmuiden, C.; Lumey, L.H.; Minihane, A.M.; Muller, M.; Murgia, C.; Radonjic, M.; Sobral, B.; West, K.P. Jr.

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

NARCIS (Netherlands)

Kaput, J.; Ommen, van B.; Kremer, B.; Priami, C.; Pontes Monteiro, J.; Morine, M.; Pepping, F.; Diaz, Z.; Fenech, M.; He, Y.; Albers, R.; Drevon, C.A.; Evelo, C.T.; Hancock, R.E.W.; Ijsselmuiden, C.; Lumey, L.H.; Minihane, A.M.; Muller, M.R.; Murgia, C.; Radonjic, M.; Sobral, B.W.S.; West Jr., K.P.

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of

Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

Directory of Open Access Journals (Sweden)

Sudin eBhattacharya

2012-12-01

Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

Top-down models in biology: explanation and control of complex living systems above the molecular level.

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Pezzulo, Giovanni; Levin, Michael

2016-11-01

It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. © 2016 The Author(s).

Systems Biology of Industrial Microorganisms

Science.gov (United States)

Papini, Marta; Salazar, Margarita; Nielsen, Jens

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Recent advances in understanding the biology of marginal zone lymphoma

Science.gov (United States)

Zucca, Emanuele

2018-01-01

There are three different marginal zone lymphomas (MZLs): the extranodal MZL of mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma), the splenic MZL, and the nodal MZL. The three MZLs share common lesions and deregulated pathways but also present specific alterations that can be used for their differential diagnosis. Although trisomies of chromosomes 3 and 18, deletions at 6q23, deregulation of nuclear factor kappa B, and chromatin remodeling genes are frequent events in all of them, the three MZLs differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel like factor 2 ( KLF2) or the receptor-type protein tyrosine phosphatase delta ( PTPRD). Since a better understanding of the molecular events underlying each subtype may have practical relevance, this review summarizes the most recent and main advances in our understanding of the genetics and biology of MZLs. PMID:29657712

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

Science.gov (United States)

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Half dozen of one, six billion of the other: What can small- and large-scale molecular systems biology learn from one another?

Science.gov (United States)

Mellis, Ian A; Raj, Arjun

2015-10-01

Small-scale molecular systems biology, by which we mean the understanding of a how a few parts work together to control a particular biological process, is predicated on the assumption that cellular regulation is arranged in a circuit-like structure. Results from the omics revolution have upset this vision to varying degrees by revealing a high degree of interconnectivity, making it difficult to develop a simple, circuit-like understanding of regulatory processes. We here outline the limitations of the small-scale systems biology approach with examples from research into genetic algorithms, genetics, transcriptional network analysis, and genomics. We also discuss the difficulties associated with deriving true understanding from the analysis of large data sets and propose that the development of new, intelligent, computational tools may point to a way forward. Throughout, we intentionally oversimplify and talk about things in which we have little expertise, and it is likely that many of our arguments are wrong on one level or another. We do believe, however, that developing a true understanding via molecular systems biology will require a fundamental rethinking of our approach, and our goal is to provoke thought along these lines. © 2015 Mellis and Raj; Published by Cold Spring Harbor Laboratory Press.

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

NARCIS (Netherlands)

Menolascina, F.; Bellomo, D.; Maiwald, T.; Bevilacqua, V.; Ciminelli, C.; Paradiso, A.; Tommasi, S.

2009-01-01

Background: Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the

Systems Biology for Organotypic Cell Cultures

Energy Technology Data Exchange (ETDEWEB)

Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

2016-08-04

Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

Tensegrity I. Cell structure and hierarchical systems biology

Science.gov (United States)

Ingber, Donald E.

2003-01-01

In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

Impact of Thermodynamic Principles in Systems Biology

NARCIS (Netherlands)

Heijnen, J.J.

2010-01-01

It is shown that properties of biological systems which are relevant for systems biology motivated mathematical modelling are strongly shaped by general thermodynamic principles such as osmotic limit, Gibbs energy dissipation, near equilibria and thermodynamic driving force. Each of these aspects

Systems Biology of Metabolism: Annual Review of Biochemistry

DEFF Research Database (Denmark)

Nielsen, Jens

2017-01-01

Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are descr...

A stratified myeloid system, the challenge of understanding macrophage diversity.

Science.gov (United States)

Geissmann, F; Mass, E

2015-12-01

The present issue of 'Seminars in Immunology' addresses the topic of macrophage biology, 100 years after the death of Elie Metchnikoff (May 1845-July 1916). As foreseen by Metchnikoff, the roles of macrophages in the maintenance of homeostasis and immunity against pathogens have become a broad and active area of investigation. We now start to realize that the myeloid system includes a multiplicity of cell types with diverse developmental origins and functions. Therefore, the textbook picture of a plastic and multifunctional macrophage does not meet the requirements of our current knowledge anymore. Further development toward a quantitative and molecular understanding of myeloid cell biology in vivo and their roles in tissue homeostasis and remodeling will benefit from taking this complexity into account. A tentative model to help in this pursuit and account for myeloid cell and macrophage diversity is discussed below. Copyright © 2016. Published by Elsevier Ltd.

Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?

Science.gov (United States)

Vazquez-Muñoz, Roberto; Borrego, Belen; Juárez-Moreno, Karla; García-García, Maritza; Mota Morales, Josué D; Bogdanchikova, Nina; Huerta-Saquero, Alejandro

2017-07-05

Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike. Copyright © 2017 Elsevier B.V. All rights reserved.

Systems Biology of Microbial Exopolysaccharides Production.

Science.gov (United States)

Ates, Ozlem

2015-01-01

Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran.

Systems biology of microbial exopolysaccharides production

Directory of Open Access Journals (Sweden)

Ozlem eAtes

2015-12-01

Full Text Available Exopolysaccharides (EPS produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture and medicine. EPSs are mainly associated with high-value applications and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore a systems-based approach constitutes an important step towards understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan and dextran.

The Systems Biology Research Tool: evolvable open-source software

Directory of Open Access Journals (Sweden)

Wright Jeremiah

2008-06-01

Full Text Available Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform called the Systems Biology Research Tool (SBRT to facilitate the computational aspects of systems biology. The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics. New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology. Conclusion The Systems Biology Research Tool represents a technological advance for systems biology. This software can be used to make sophisticated computational techniques accessible to everyone (including those with no programming ability, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

Understanding schizophrenia as a disorder of consciousness: biological correlates and translational implications from quantum theory perspectives.

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Venkatasubramanian, Ganesan

2015-04-30

From neurophenomenological perspectives, schizophrenia has been conceptualized as "a disorder with heterogeneous manifestations that can be integrally understood to involve fundamental perturbations in consciousness". While these theoretical constructs based on consciousness facilitate understanding the 'gestalt' of schizophrenia, systematic research to unravel translational implications of these models is warranted. To address this, one needs to begin with exploration of plausible biological underpinnings of "perturbed consciousness" in schizophrenia. In this context, an attractive proposition to understand the biology of consciousness is "the orchestrated object reduction (Orch-OR) theory" which invokes quantum processes in the microtubules of neurons. The Orch-OR model is particularly important for understanding schizophrenia especially due to the shared 'scaffold' of microtubules. The initial sections of this review focus on the compelling evidence to support the view that "schizophrenia is a disorder of consciousness" through critical summary of the studies that have demonstrated self-abnormalities, aberrant time perception as well as dysfunctional intentional binding in this disorder. Subsequently, these findings are linked with 'Orch-OR theory' through the research evidence for aberrant neural oscillations as well as microtubule abnormalities observed in schizophrenia. Further sections emphasize the applicability and translational implications of Orch-OR theory in the context of schizophrenia and elucidate the relevance of quantum biology to understand the origins of this puzzling disorder as "fundamental disturbances in consciousness".

On the interplay between mathematics and biology: hallmarks toward a new systems biology.

Science.gov (United States)

Bellomo, Nicola; Elaiw, Ahmed; Althiabi, Abdullah M; Alghamdi, Mohammed Ali

2015-03-01

This paper proposes a critical analysis of the existing literature on mathematical tools developed toward systems biology approaches and, out of this overview, develops a new approach whose main features can be briefly summarized as follows: derivation of mathematical structures suitable to capture the complexity of biological, hence living, systems, modeling, by appropriate mathematical tools, Darwinian type dynamics, namely mutations followed by selection and evolution. Moreover, multiscale methods to move from genes to cells, and from cells to tissue are analyzed in view of a new systems biology approach. Copyright © 2014 Elsevier B.V. All rights reserved.

Computational Modeling of Biological Systems From Molecules to Pathways

CERN Document Server

2012-01-01

Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

Systems Biology — the Broader Perspective

Directory of Open Access Journals (Sweden)

Jonathan Bard

2013-06-01

Full Text Available Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] . Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.

Multidisciplinary approaches to understanding collective cell migration in developmental biology.

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Schumacher, Linus J; Kulesa, Paul M; McLennan, Rebecca; Baker, Ruth E; Maini, Philip K

2016-06-01

Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. © 2016 The Authors.

Systems Biology and Stem Cell Pluripotency

DEFF Research Database (Denmark)

Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

2016-01-01

Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

Optoelectronic system and apparatus for connection to biological systems

Science.gov (United States)

Okandan, Murat; Nielson, Gregory N.

2018-03-06

The present invention relates to a biological probe structure, as well as apparatuses, systems, and methods employing this structure. In particular embodiments, the structure includes a hermetically sealed unit configured to receive and transmit one or more optical signals. Furthermore, the structure can be implanted subcutaneously and interrogated externally. In this manner, a minimally invasive method can be employed to detect, treat, and/or assess the biological target. Additional methods and systems are also provided.

The female gametophyte: an emerging model for cell type-specific systems biology in plant development

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Marc William Schmid

2015-11-01

Full Text Available Systems biology, a holistic approach describing a system emerging from the interactions of its molecular components, critically depends on accurate qualitative determination and quantitative measurements of these components. Development and improvement of large-scale profiling methods (omics now facilitates comprehensive measurements of many relevant molecules. For multicellular organisms, such as animals, fungi, algae, and plants, the complexity of the system is augmented by the presence of specialized cell types and organs, and a complex interplay within and between them. Cell type-specific analyses are therefore crucial for the understanding of developmental processes and environmental responses. This review first gives an overview of current methods used for large-scale profiling of specific cell types exemplified by recent advances in plant biology. The focus then lies on suitable model systems to study plant development and cell type specification. We introduce the female gametophyte of flowering plants as an ideal model to study fundamental developmental processes. Moreover, the female reproductive lineage is of importance for the emergence of evolutionary novelties such as an unequal parental contribution to the tissue nurturing the embryo or the clonal production of seeds by asexual reproduction (apomixis. Understanding these processes is not only interesting from a developmental or evolutionary perspective, but bears great potential for further crop improvement and the simplification of breeding efforts. We finally highlight novel methods, which are already available or which will likely soon facilitate large-scale profiling of the specific cell types of the female gametophyte in both model and non-model species. We conclude that it may take only few years until an evolutionary systems biology approach toward female gametogenesis may decipher some of its biologically most interesting and economically most valuable processes.

A review of imaging techniques for systems biology

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Po Ming J

2008-08-01

Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

Understanding the Reading Attributes and Their Cognitive Relationships on a High-Stakes Biology Assessment

Science.gov (United States)

Rawlusyk, Kevin James

Test items used to assess learners' knowledge on high-stakes science examinations contain contextualized questions that unintentionally assess reading skill along with conceptual knowledge. Therefore, students who are not proficient readers are unable to comprehend the text within the test item to demonstrate effectively their level of science knowledge. The purpose of this quantitative study was to understand what reading attributes were required to successfully answer the Biology 30 Diploma Exam. Furthermore, the research sought to understand the cognitive relationships among the reading attributes through quantitative analysis structured by the Attribute Hierarchy Model (AHM). The research consisted of two phases: (1) Cognitive development, where the cognitive attributes of the Biology 30 Exam were specified and hierarchy structures were developed; and (2) Psychometric analysis, that statistically tested the attribute hierarchy using the Hierarchy Consistency Index (HCI), and calculate attribute probabilities. Phase one of the research used January 2011, Biology 30 Diploma Exam, while phase two accessed archival data for the 9985 examinees who took the assessment on January 24th, 2011. Phase one identified ten specific reading attributes, of which five were identified as unique subsets of vocabulary, two were identified as reading visual representations, and three corresponded to general reading skills. Four hierarchical cognitive model were proposed then analyzed using the HCI as a mechanism to explain the relationship among the attributes. Model A had the highest HCI value (0.337), indicating an overall poor data fit, yet for the top achieving examinees the model had an excellent model fit with an HCI value of 0.888, and for examinees that scored over 60% there was a moderate model fit (HCI = 0.592). Linear regressions of the attribute probability estimates suggest that there is a cognitive relationship among six of the ten reading attributes (R2 = 0.958 and 0

The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria

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Meghan Zuck

2017-11-01

Full Text Available Despite global eradication efforts over the past century, malaria remains a devastating public health burden, causing almost half a million deaths annually (WHO, 2016. A detailed understanding of the mechanisms that control malaria infection has been hindered by technical challenges of studying a complex parasite life cycle in multiple hosts. While many interventions targeting the parasite have been implemented, the complex biology of Plasmodium poses a major challenge, and must be addressed to enable eradication. New approaches for elucidating key host-parasite interactions, and predicting how the parasite will respond in a variety of biological settings, could dramatically enhance the efficacy and longevity of intervention strategies. The field of systems biology has developed methodologies and principles that are well poised to meet these challenges. In this review, we focus our attention on the Liver Stage of the Plasmodium lifecycle and issue a “call to arms” for using systems biology approaches to forge a new era in malaria research. These approaches will reveal insights into the complex interplay between host and pathogen, and could ultimately lead to novel intervention strategies that contribute to malaria eradication.

Programming Morphogenesis through Systems and Synthetic Biology.

Science.gov (United States)

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

A system for success: BMC Systems Biology, a new open access journal

OpenAIRE

Webb Penelope A; Hodgkinson Matt J

2007-01-01

Abstract BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

Systems biology of neutrophil differentiation and immune response

DEFF Research Database (Denmark)

Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

2005-01-01

Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

Biological Potential in Serpentinizing Systems

Science.gov (United States)

Hoehler, Tori M.

2016-01-01

Generation of the microbial substrate hydrogen during serpentinization, the aqueous alteration of ultramafic rocks, has focused interest on the potential of serpentinizing systems to support biological communities or even the origin of life. However the process also generates considerable alkalinity, a challenge to life, and both pH and hydrogen concentrations vary widely across natural systems as a result of different host rock and fluid composition and differing physical and hydrogeologic conditions. Biological potential is expected to vary in concert. We examined the impact of such variability on the bioenergetics of an example metabolism, methanogenesis, using a cell-scale reactive transport model to compare rates of metabolic energy generation as a function of physicochemical environment. Potential rates vary over more than 5 orders of magnitude, including bioenergetically non-viable conditions, across the range of naturally occurring conditions. In parallel, we assayed rates of hydrogen metabolism in wells associated with the actively serpentinizing Coast Range Ophiolite, which includes conditions more alkaline and considerably less reducing than is typical of serpentinizing systems. Hydrogen metabolism is observed at pH approaching 12 but, consistent with the model predictions, biological methanogenesis is not observed.

BetaWB - A language for modular representation of biological systems

DEFF Research Database (Denmark)

Ihekwaba, Adoha; Larcher, Roberto; Mardare, Radu Iulian

2007-01-01

A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007......A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007...

Systems biology perspectives on minimal and simpler cells.

Science.gov (United States)

Xavier, Joana C; Patil, Kiran Raosaheb; Rocha, Isabel

2014-09-01

The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Systems Biology Perspectives on Minimal and Simpler Cells

Science.gov (United States)

Xavier, Joana C.; Patil, Kiran Raosaheb

2014-01-01

SUMMARY The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. PMID:25184563

Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions.

Science.gov (United States)

Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long

By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

Science.gov (United States)

Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

2009-10-15

Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated

Student Teachers' Ways of Thinking and Ways of Understanding Digestion and the Digestive System in Biology

Science.gov (United States)

Çimer, Sabiha Odabasi; Ursavas, Nazihan

2012-01-01

The purpose of this study was to identify the ways in which student teachers understand digestion and the digestive system and, subsequently, their ways of thinking, as reflected in their problem solving approaches and the justification schemes that they used to validate their claims. For this purpose, clinical interviews were conducted with 10…

Yeast systems biology to unravel the network of life

DEFF Research Database (Denmark)

Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

2006-01-01

Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...... laboratory has access to all the necessary competences. For this reason the Yeast Systems Biology Network (YSBN) has been established. YSBN will coordinate research efforts, in yeast systems biology and, through the recently obtained EU funding for a Coordination Action, it will be possible to set...

3S - Systematic, systemic, and systems biology and toxicology.

Science.gov (United States)

Smirnova, Lena; Kleinstreuer, Nicole; Corvi, Raffaella; Levchenko, Andre; Fitzpatrick, Suzanne C; Hartung, Thomas

2018-01-01

A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling. Toxicology contains the somewhat arbitrary subclass "systemic toxicities"; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca-pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized. We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal-lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

A dedicated database system for handling multi-level data in systems biology.

Science.gov (United States)

Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging. To overcome this, we designed and developed a dedicated database system that can serve and solve the vital issues in data management and hereby facilitate data integration, modeling and analysis in systems biology within a sole database. In addition, a yeast data repository was implemented as an integrated database environment which is operated by the database system. Two applications were implemented to demonstrate extensibility and utilization of the system. Both illustrate how the user can access the database via the web query function and implemented scripts. These scripts are specific for two sample cases: 1) Detecting the pheromone pathway in protein interaction networks; and 2) Finding metabolic reactions regulated by Snf1 kinase. In this study we present the design of database system which offers an extensible environment to efficiently capture the majority of biological entities and relations encountered in systems biology. Critical functions and control processes were designed and implemented to ensure consistent, efficient, secure and reliable transactions. The two sample cases on the yeast integrated data clearly demonstrate the value of a sole database environment for systems biology research.

Strategies for structuring interdisciplinary education in Systems Biology

DEFF Research Database (Denmark)

Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure

2016-01-01

function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material...... and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active...... performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii...

Multilayer microfluidic systems with indium-tin-oxide microelectrodes for studying biological cells

International Nuclear Information System (INIS)

Wu, Hsiang-Chiu; Chen, Hsin; Lyau, Jia-Bo; Lin, Min-Hsuan; Chuang, Yung-Jen

2017-01-01

Contemporary semiconductor and micromachining technologies have been exploited to develop lab-on-a-chip microsystems, which enable parallel and efficient experiments in molecular and cellular biology. In these microlab systems, microfluidics play an important role for automatic transportation or immobilization of cells and bio-molecules, as well as for separation or mixing of different chemical reagents. However, seldom microlab systems allow both morphology and electrophysiology of biological cells to be studied in situ . This kind of study is important, for example, for understanding how neuronal networks grow in response to environmental stimuli. To fulfill this application need, this paper investigates the possibility of fabricating multi-layer photoresists as microfluidic systems directly above a glass substrate with indium-tin-oxide (ITO) electrodes. The microfluidic channels are designed to guide and trap biological cells on top of ITO electrodes, through which the electrical activities of cells can be recorded or elicited. As both the microfluidic system and ITO electrodes are transparent, the cellular morphology is observable easily during electrophysiological studies. Two fabrication processes are proposed and compared. One defines the structure and curing depth of each photoresist layer simply by controlling the exposure time in lithography, while the other further utilizes a sacrificial layer to defines the structure of the bottom layer. The fabricated microfluidic system is proved bio-compatible and able to trap blood cells or neurons. Therefore, the proposed microsystem will be useful for studying cultured cells efficiently in applications such as drug-screening. (paper)

Final report for Conference Support Grant "From Computational Biophysics to Systems Biology - CBSB12"

Energy Technology Data Exchange (ETDEWEB)

Hansmann, Ulrich H.E.

2012-07-02

This report summarizes the outcome of the international workshop From Computational Biophysics to Systems Biology (CBSB12) which was held June 3-5, 2012, at the University of Tennessee Conference Center in Knoxville, TN, and supported by DOE through the Conference Support Grant 120174. The purpose of CBSB12 was to provide a forum for the interaction between a data-mining interested systems biology community and a simulation and first-principle oriented computational biophysics/biochemistry community. CBSB12 was the sixth in a series of workshops of the same name organized in recent years, and the second that has been held in the USA. As in previous years, it gave researchers from physics, biology, and computer science an opportunity to acquaint each other with current trends in computational biophysics and systems biology, to explore venues of cooperation, and to establish together a detailed understanding of cells at a molecular level. The conference grant of $10,000 was used to cover registration fees and provide travel fellowships to selected students and postdoctoral scientists. By educating graduate students and providing a forum for young scientists to perform research into the working of cells at a molecular level, the workshop adds to DOE's mission of paving the way to exploit the abilities of living systems to capture, store and utilize energy.

1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

International Nuclear Information System (INIS)

Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

2011-01-01

The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

Redefining plant systems biology: from cell to ecosystem

NARCIS (Netherlands)

Keurentjes, J.J.B.; Angenent, G.C.; Dicke, M.; Martins Dos Santos, V.A.P.; Molenaar, J.; Van der Putten, W.H.; de Ruiter, P.C.; Struik, P.C.; Thomma, B.P.H.J.

2011-01-01

Molecular biologists typically restrict systems biology to cellular levels. By contrast, ecologists define biological systems as communities of interacting individuals at different trophic levels that process energy, nutrient and information flows. Modern plant breeding needs to increase

Cellular respiration: replicating in vivo systems biology for in ...

Science.gov (United States)

This editorial develops a philosophy for expanding the scope of Journal of Breath Research (JBR) into the realm of cellular level study, and links certain topics back to more traditional systemic research for understanding human health based on exhaled breath constituents. The express purpose is to provide a publication outlet for novel breath related research that includes in vitro studies, especially those that explore the biological origin and expression of compounds that may ultimately influence the constituents of exhaled breath. The new topics include all manner of methods and instrumentations for making in vivo and in vitro measurements, the use of different biological media (blood, urine saliva, swabs) including human and microbial cell-lines, in vitro kinetic studies of metabolism, and advances in ex vivo methods for maintaining metabolic competency and viability of biological samples. Traditionally, JBR has published articles on human breath analysis for diagnosing disease, tracking health state, assessing the dose and effect of exogenous chemicals, and contributions of malodorous compounds from the oral/nasal cavity. These have also included research describing novel sampling and analytical technologies, most notably those implementing mass spectrometry, chemical sensors and optical measurement instrumentation (Amann and Smith 2013). The journal’s original scope has also embraced animal models as surrogates for human sampling, new mathematical and

Multi-level and hybrid modelling approaches for systems biology.

Science.gov (United States)

Bardini, R; Politano, G; Benso, A; Di Carlo, S

2017-01-01

During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself. In systems biology, biological information often comes from overlapping but different scientific domains, each one having its own way of representing phenomena under study. That is, the different parts of the system to be modelled may be described with different formalisms. For a model to have improved accuracy and capability for making a good knowledge base, it is good to comprise different system levels, suitably handling the relative formalisms. Models which are both multi-level and hybrid satisfy both these requirements, making a very useful tool in computational systems biology. This paper reviews some of the main contributions in this field.

Electromagnetic fields in biological systems

National Research Council Canada - National Science Library

Lin, James C

2012-01-01

"Focusing on exposure, induced fields, and absorbed energy, this volume covers the interaction of electromagnetic fields and waves with biological systems, spanning static fields to terahertz waves...

Tunable promoters in synthetic and systems biology

DEFF Research Database (Denmark)

Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

2012-01-01

in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

Systems biology solutions for biochemical production challenges

DEFF Research Database (Denmark)

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

2017-01-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...... characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity...... compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains...

Biological neural networks as model systems for designing future parallel processing computers

Science.gov (United States)

Ross, Muriel D.

1991-01-01

One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

High definition for systems biology of microbial communities: metagenomics gets genome-centric and strain-resolved.

Science.gov (United States)

Turaev, Dmitrij; Rattei, Thomas

2016-06-01

The systems biology of microbial communities, organismal communities inhabiting all ecological niches on earth, has in recent years been strongly facilitated by the rapid development of experimental, sequencing and data analysis methods. Novel experimental approaches and binning methods in metagenomics render the semi-automatic reconstructions of near-complete genomes of uncultivable bacteria possible, while advances in high-resolution amplicon analysis allow for efficient and less biased taxonomic community characterization. This will also facilitate predictive modeling approaches, hitherto limited by the low resolution of metagenomic data. In this review, we pinpoint the most promising current developments in metagenomics. They facilitate microbial systems biology towards a systemic understanding of mechanisms in microbial communities with scopes of application in many areas of our daily life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognition and Rhetoric: Biological Basis of Meaning and Understanding

Directory of Open Access Journals (Sweden)

Francisco Arenas-Dolz

2017-02-01

Full Text Available The aim of this paper is twofold: on the one hand, to explore those approaches that understand cognitive processes as embodied and as a result of our interaction with the environment, and not merely as as a information processing system; and, on the other hand, to show their connexion with the neurophysiological mechanisms underlying meaning and understanding, giving and overview of some of the insights from recent studies in neurorhetorics.

Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

Directory of Open Access Journals (Sweden)

Gavin C. Bowick

2010-01-01

Full Text Available Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.

The aims of systems biology: between molecules and organisms.

Science.gov (United States)

Noble, D

2011-05-01

The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

Science.gov (United States)

Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

2010-01-01

The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

The Relationship between Biology Teachers' Understanding of the Nature of Science and the Understanding and Acceptance of the Theory of Evolution

Science.gov (United States)

Cofré, Hernán; Cuevas, Emilia; Becerra, Beatriz

2017-01-01

Despite the importance of the theory of evolution (TE) to scientific knowledge, a number of misconceptions continue to be found among biology teachers. In this context, the first objective of this study was to identify the impact of professional development programme (PDP) on teachers' understanding of nature of science (NOS) and evolution and on…

Systems Biology: Impressions from a Newcomer Graduate Student in 2016

Science.gov (United States)

Simpson, Melanie Rae

2016-01-01

As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in…

Mathematical methods in systems biology.

Science.gov (United States)

Kashdan, Eugene; Duncan, Dominique; Parnell, Andrew; Schattler, Heinz

2016-12-01

The editors of this Special Issue of Mathematical Biosciences and Engineering were the organizers for the Third International Workshop "Mathematical Methods in System Biology" that took place on June 15-18, 2015 at the University College Dublin in Ireland. As stated in the workshop goals, we managed to attract a good mix of mathematicians and statisticians working on biological and medical applications with biologists and clinicians interested in presenting their challenging problems and looking to find mathematical and statistical tools for their solutions.

Nanoscale technology in biological systems

CERN Document Server

Greco, Ralph S; Smith, R Lane

2004-01-01

Reviewing recent accomplishments in the field of nanobiology Nanoscale Technology in Biological Systems introduces the application of nanoscale matrices to human biology. It focuses on the applications of nanotechnology fabrication to biomedical devices and discusses new physical methods for cell isolation and manipulation and intracellular communication at the molecular level. It also explores the application of nanobiology to cardiovascular diseases, oncology, transplantation, and a range of related disciplines. This book build a strong background in nanotechnology and nanobiology ideal for

The relationship between biology teachers' understanding of the nature of science and the understanding and acceptance of the theory of evolution

Science.gov (United States)

Cofré, Hernán; Cuevas, Emilia; Becerra, Beatriz

2017-11-01

Despite the importance of the theory of evolution (TE) to scientific knowledge, a number of misconceptions continue to be found among biology teachers. In this context, the first objective of this study was to identify the impact of professional development programme (PDP) on teachers' understanding of nature of science (NOS) and evolution and on the acceptance of this theory. Its second objective was to study the relationship among these variables. Three instruments were used to quantify these variables: the Views of the Nature of Science Version D (VNOS D+), the Assessing Contextual Reasoning about Natural Selection (ACORN), and the Measure of Acceptance of Theory of Evolution (MATE). The results indicate that the PDP had a positive impact on teachers, significantly improving their understanding of the NOS and natural selection, as well as their acceptance of the TE. Furthermore, a positive correlation between the understanding of the NOS obtained by teachers in the first part of the PDP and the understanding and acceptance of evolution that these teachers showed at the end of the programme was determined. However, no relationship between an understanding of the NOS and gains in the understanding and acceptance of evolution was found.

Unleashing the potential of the root hair cell as a single plant cell type model in root systems biology

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Zhenzhen eQiao

2013-11-01

Full Text Available Plant root is an organ composed of multiple cell types with different functions. This multicellular complexity limits our understanding of root biology because –omics studies performed at the level of the entire root reflect the average responses of all cells composing the organ. To overcome this difficulty and allow a more comprehensive understanding of root cell biology, an approach is needed that would focus on one single cell type in the plant root. Because of its biological functions (i.e. uptake of water and various nutrients; primary site of infection by nitrogen-fixing bacteria in legumes, the root hair cell is an attractive single cell model to study root cell response to various stresses and treatments. To fully study their biology, we have recently optimized procedures in obtaining root hair cell samples. We culture the plants using an ultrasound aeroponic system maximizing root hair cell density on the entire root systems and allowing the homogeneous treatment of the root system. We then isolate the root hair cells in liquid nitrogen. Isolated root hair yields could be up to 800 to 1000 mg of plant cells from 60 root systems. Using soybean as a model, the purity of the root hair was assessed by comparing the expression level of genes previously identified as soybean root hair specific between preparations of isolated root hair cells and stripped roots, roots devoid in root hairs. Enlarging our tests to include other plant species, our results support the isolation of large quantities of highly purified root hair cells which is compatible with a systems biology approach.

A data integration approach for cell cycle analysis oriented to model simulation in systems biology

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Mosca Ettore

2007-08-01

Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

Modeling of biological intelligence for SCM system optimization.

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Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

2012-01-01

This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

Modeling of Biological Intelligence for SCM System Optimization

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Shengyong Chen

2012-01-01

Full Text Available This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

Modeling of Biological Intelligence for SCM System Optimization

Science.gov (United States)

Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

2012-01-01

This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms. PMID:22162724

Systems biology at work

NARCIS (Netherlands)

Martins Dos Santos, V.A.P.; Damborsky, J.

2010-01-01

In his editorial overview for the 2008 Special Issue on this topic, the late Jaroslav Stark pointedly noted that systems biology is no longer a niche pursuit, but a recognized discipline in its own right “noisily” coming of age [1]. Whilst general underlying principles and basic techniques are now

Joining Forces: The Chemical Biology-Medicinal Chemistry Continuum.

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Plowright, Alleyn T; Ottmann, Christian; Arkin, Michelle; Auberson, Yves P; Timmerman, Henk; Waldmann, Herbert

2017-09-21

The scientific advances being made across all disciplines are creating ever-increasing opportunities to enhance our knowledge of biological systems and how they relate to human disease. One of the central driving forces in discovering new medicines is medicinal chemistry, where the design and synthesis of novel compounds has led to multiple drugs. Chemical biology, sitting at the interface of many disciplines, has now emerged as a major contributor to the understanding of biological systems and is becoming an integral part of drug discovery. Bringing chemistry and biology much closer and blurring the boundaries between disciplines is creating new opportunities to probe and understand biology; both disciplines play key roles and need to join forces and work together effectively to synergize their impact. The power of chemical biology will then reach its full potential and drive innovation, leading to the discovery of transformative medicines to treat patients. Advances in cancer biology and drug discovery highlight this potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

International Nuclear Information System (INIS)

Eschrich, Steven; Zhang Hongling; Zhao Haiyan; Boulware, David; Lee, Ji-Hyun; Bloom, Gregory; Torres-Roca, Javier F.

2009-01-01

Purpose: The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials: Radiosensitivity, as represented by the survival fraction at 2 Gy was modeled in 48 human cancer cell lines. We applied a linear regression algorithm that integrates gene expression with biological variables, including ras status (mut/wt), tissue of origin and p53 status (mut/wt). Results: The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression analysis. This network was reduced to a 10-hub network that includes c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1, and IRF1. Nine targets associated with radiosensitization drugs are linked to the network, demonstrating clinical relevance. Furthermore, the model identified four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis, as was the tissue of origin, and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included DNA repair, cell cycle, apoptosis, and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon, and breast cancers. Conclusion: We have developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We believe this platform will play a central role in the integration of biology into clinical radiation oncology practice.

The Effects of Case-Based Instruction on Undergraduate Biology Students' Understanding of the Nature of Science

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Burniston, Amy Lucinda

Undergraduate science education is currently seeing a dramatic pedagogical push towards teaching the philosophies underpinning science as well as an increase in strategies that employ active learning. Many active learning strategies stem from constructivist ideals and have been shown to affect a student's understanding of how science operates and its impact on society- commonly referred to as the nature of science (NOS). One particular constructivist teaching strategy, case-based instruction (CBI), has been recommended by researchers and science education reformists as an effective instructional strategy for teaching NOS. Furthermore, when coupled with explicit-reflective instruction, CBI has been found to significantly increasing understanding of NOS in elementary and secondary students. However, few studies aimed their research on CBI and NOS towards higher education. Thus, this study uses a quasi-experimental, nonequivalent group design to study the effects of CBI on undergraduate science students understandings of NOS. Undergraduate biology student's understanding of NOS were assessed using the Views of Science Education (VOSE) instrument pre and post CBI intervention in Cellular and Molecular Biology and Human Anatomy and Physiology II. Data analysis indicated statistically significant differences between students NOS scores in experimental versus control sections for both courses, with experimental groups obtaining higher posttest scores. The results of this study indicate that undergraduate male and female students have similarly poor understandings of NOS and the use of historical case based instruction can be used as a means to increase undergraduate understanding of NOS.

Supporting cognition in systems biology analysis: findings on users' processes and design implications.

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Mirel, Barbara

2009-02-13

Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation. Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling. As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

Systems biology for molecular life sciences and its impact in biomedicine.

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Medina, Miguel Ángel

2013-03-01

Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

“Gestaltomics”: Systems Biology Schemes for the Study of Neuropsychiatric Diseases

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Nora A. Gutierrez Najera

2017-05-01

Full Text Available The integration of different sources of biological information about what defines a behavioral phenotype is difficult to unify in an entity that reflects the arithmetic sum of its individual parts. In this sense, the challenge of Systems Biology for understanding the “psychiatric phenotype” is to provide an improved vision of the shape of the phenotype as it is visualized by “Gestalt” psychology, whose fundamental axiom is that the observed phenotype (behavior or mental disorder will be the result of the integrative composition of every part. Therefore, we propose the term “Gestaltomics” as a term from Systems Biology to integrate data coming from different sources of information (such as the genome, transcriptome, proteome, epigenome, metabolome, phenome, and microbiome. In addition to this biological complexity, the mind is integrated through multiple brain functions that receive and process complex information through channels and perception networks (i.e., sight, ear, smell, memory, and attention that in turn are programmed by genes and influenced by environmental processes (epigenetic. Today, the approach of medical research in human diseases is to isolate one disease for study; however, the presence of an additional disease (co-morbidity or more than one disease (multimorbidity adds complexity to the study of these conditions. This review will present the challenge of integrating psychiatric disorders at different levels of information (Gestaltomics. The implications of increasing the level of complexity, for example, studying the co-morbidity with another disease such as cancer, will also be discussed.

Plant Systems Biology (editorial)

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In June 2003, Plant Physiology published an Arabidopsis special issue devoted to plant systems biology. The intention of Natasha Raikhel and Gloria Coruzzi, the two editors of this first-of-its-kind issue, was ‘‘to help nucleate this new effort within the plant community’’ as they considered that ‘‘...

A day of systems and synthetic biology for non-experts: reflections on day 1 of the EMBL/EMBO joint conference on Science and Society.

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Moore, Andrew

2009-01-01

From understanding ageing to the creation of artificial membrane-bounded 'organisms', systems biology and synthetic biology are seen as the latest revolutions in the life sciences. They certainly represent a major change of gear, but paradigm shifts? This is open to debate, to say the least. For scientists they open up exciting ways of studying living systems, of formulating the 'laws of life', and the relationship between the origin of life, evolution and artificial biological systems. However, the ethical and societal considerations are probably indistinguishable from those of human genetics and genetically modified organisms. There are some tangible developments just around the corner for society, and as ever, our ability to understand the consequences of, and manage, our own progress lags far behind our technological abilities. Furthermore our educational systems are doing a bad job of preparing the next generation of scientists and non-scientists.

Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

Science.gov (United States)

De Domenico, Manlio

2018-03-01

Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

Understanding the biological activity of high rate algae ponds through the calculation of oxygen balances.

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Arbib, Zouhayr; de Godos Crespo, Ignacio; Corona, Enrique Lara; Rogalla, Frank

2017-06-01

Microalgae culture in high rate algae ponds (HRAP) is an environmentally friendly technology for wastewater treatment. However, for the implementation of these systems, a better understanding of the oxygenation potential and the influence of climate conditions is required. In this work, the rates of oxygen production, consumption, and exchange with the atmosphere were calculated under varying conditions of solar irradiance and dilution rate during six months of operation in a real scale unit. This analysis allowed determining the biological response of these dynamic systems. The rates of oxygen consumption measured were considerably higher than the values calculated based on the organic loading rate. The response to light intensity in terms of oxygen production in the bioreactor was described with one of the models proposed for microalgae culture in dense concentrations. This model is based on the availability of light inside the culture and the specific response of microalgae to this parameter. The specific response to solar radiation intensity showed a reasonable stability in spite of the fluctuations due to meteorological conditions. The methodology developed is a useful tool for optimization and prediction of the performance of these systems.

Systems biology solutions for biochemical production challenges.

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Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

2017-06-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

GPSR: A Resource for Genomics Proteomics and Systems Biology

Indian Academy of Sciences (India)

GPSR: A Resource for Genomics Proteomics and Systems Biology · Simple Calculation Programs for Biology Immunological Methods · Simple Calculation Programs for Biology Methods in Molecular Biology · Simple Calculation Programs for Biology Other Methods · PowerPoint Presentation · Slide 6 · Slide 7 · Prediction of ...

Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems

Science.gov (United States)

Rivera-Jacquez, Hector J.; Masunov, Artëm E.

2018-06-01

Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.

TissueCypher™: A systems biology approach to anatomic pathology

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Jeffrey W Prichard

2015-01-01

Full Text Available Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22 and Barrett's with high-grade dysplasia (HGD, n = 17. Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional

From biological and social network metaphors to coupled bio-social wireless networks

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Barrett, Christopher L.; Eubank, Stephen; Anil Kumar, V.S.; Marathe, Madhav V.

2010-01-01

Biological and social analogies have been long applied to complex systems. Inspiration has been drawn from biological solutions to solve problems in engineering products and systems, ranging from Velcro to camouflage to robotics to adaptive and learning computing methods. In this paper, we present an overview of recent advances in understanding biological systems as networks and use this understanding to design and analyse wireless communication networks. We expand on two applications, namely cognitive sensing and control and wireless epidemiology. We discuss how our work in these two applications is motivated by biological metaphors. We believe that recent advances in computing and communications coupled with advances in health and social sciences raise the possibility of studying coupled bio-social communication networks. We argue that we can better utilise the advances in our understanding of one class of networks to better our understanding of the other. PMID:21643462

Biological and geophysical feedbacks with fire in the Earth system

Science.gov (United States)

Archibald, S.; Lehmann, C. E. R.; Belcher, C. M.; Bond, W. J.; Bradstock, R. A.; Daniau, A.-L.; Dexter, K. G.; Forrestel, E. J.; Greve, M.; He, T.; Higgins, S. I.; Hoffmann, W. A.; Lamont, B. B.; McGlinn, D. J.; Moncrieff, G. R.; Osborne, C. P.; Pausas, J. G.; Price, O.; Ripley, B. S.; Rogers, B. M.; Schwilk, D. W.; Simon, M. F.; Turetsky, M. R.; Van der Werf, G. R.; Zanne, A. E.

2018-03-01

Roughly 3% of the Earth’s land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels—namely plants and their litter—that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.

It's the System, Stupid: How Systems Biology Is Transforming.

Science.gov (United States)

2010-01-01

So far, little is known about systems biology and its potential for changing how we diagnose and treat disease. That will change soon, say the systems experts, who advise payers to begin learning now about how it could make healthcare efficient.

Future Science Teachers' Understandings of Diffusion and Osmosis Concepts

Science.gov (United States)

Tomazic, Iztok; Vidic, Tatjana

2012-01-01

The concepts of diffusion and osmosis cross the disciplinary boundaries of physics, chemistry and biology. They are important for understanding how biological systems function. Since future (pre-service) science teachers in Slovenia encounter both concepts at physics, chemistry and biology courses during their studies, we assessed the first-,…

The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

Science.gov (United States)

Hucka, Michael; Bergmann, Frank T; Hoops, Stefan; Keating, Sarah M; Sahle, Sven; Schaff, James C; Smith, Lucian P; Wilkinson, Darren J

2015-09-04

Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

The Biology of Behaviour.

Science.gov (United States)

Broom, D. M.

1981-01-01

Discusses topics to aid in understanding animal behavior, including the value of the biological approach to psychology, functional systems, optimality and fitness, universality of environmental effects on behavior, and evolution of social behavior. (DS)

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

Science.gov (United States)

Demongeot, Jacques; Goles, Eric; Morvan, Michel; Noual, Mathilde; Sené, Sylvain

2010-01-01

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally. PMID:20700525

Attraction basins as gauges of robustness against boundary conditions in biological complex systems.

Directory of Open Access Journals (Sweden)

Jacques Demongeot

Full Text Available One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally.

An online model composition tool for system biology models.

Science.gov (United States)

Coskun, Sarp A; Cicek, A Ercument; Lai, Nicola; Dash, Ranjan K; Ozsoyoglu, Z Meral; Ozsoyoglu, Gultekin

2013-09-05

There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user's input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well.

Structure, function, and behaviour of computational models in systems biology.

Science.gov (United States)

Knüpfer, Christian; Beckstein, Clemens; Dittrich, Peter; Le Novère, Nicolas

2013-05-31

Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such "bio-models" necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. We present a conceptual framework - the meaning facets - which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model's components (structure), the meaning of the model's intended use (function), and the meaning of the model's dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

SEEK: a systems biology data and model management platform.

Science.gov (United States)

Wolstencroft, Katherine; Owen, Stuart; Krebs, Olga; Nguyen, Quyen; Stanford, Natalie J; Golebiewski, Martin; Weidemann, Andreas; Bittkowski, Meik; An, Lihua; Shockley, David; Snoep, Jacky L; Mueller, Wolfgang; Goble, Carole

2015-07-11

Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug-in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and

Synthetic biology: an emerging engineering discipline.

Science.gov (United States)

Cheng, Allen A; Lu, Timothy K

2012-01-01

Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

Conceptual modeling in systems biology fosters empirical findings: the mRNA lifecycle.

Directory of Open Access Journals (Sweden)

Dov Dori

Full Text Available One of the main obstacles to understanding complex biological systems is the extent and rapid evolution of information, way beyond the capacity individuals to manage and comprehend. Current modeling approaches and tools lack adequate capacity to model concurrently structure and behavior of biological systems. Here we propose Object-Process Methodology (OPM, a holistic conceptual modeling paradigm, as a means to model both diagrammatically and textually biological systems formally and intuitively at any desired number of levels of detail. OPM combines objects, e.g., proteins, and processes, e.g., transcription, in a way that is simple and easily comprehensible to researchers and scholars. As a case in point, we modeled the yeast mRNA lifecycle. The mRNA lifecycle involves mRNA synthesis in the nucleus, mRNA transport to the cytoplasm, and its subsequent translation and degradation therein. Recent studies have identified specific cytoplasmic foci, termed processing bodies that contain large complexes of mRNAs and decay factors. Our OPM model of this cellular subsystem, presented here, led to the discovery of a new constituent of these complexes, the translation termination factor eRF3. Association of eRF3 with processing bodies is observed after a long-term starvation period. We suggest that OPM can eventually serve as a comprehensive evolvable model of the entire living cell system. The model would serve as a research and communication platform, highlighting unknown and uncertain aspects that can be addressed empirically and updated consequently while maintaining consistency.

Exploring Synthetic and Systems Biology at the University of Edinburgh.

Science.gov (United States)

Fletcher, Liz; Rosser, Susan; Elfick, Alistair

2016-06-15

The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Unleashing elastic energy: dynamics of energy release in rubber bands and impulsive biological systems

Science.gov (United States)

Ilton, Mark; Cox, Suzanne; Egelmeers, Thijs; Patek, S. N.; Crosby, Alfred J.

Impulsive biological systems - which include mantis shrimp, trap-jaw ants, and venus fly traps - can reach high speeds by using elastic elements to store and rapidly release energy. The material behavior and shape changes critical to achieving rapid energy release in these systems are largely unknown due to limitations of materials testing instruments operating at high speed and large displacement. In this work, we perform fundamental, proof-of-concept measurements on the tensile retraction of elastomers. Using high speed imaging, the kinematics of retraction are measured for elastomers with varying mechanical properties and geometry. Based on the kinematics, the rate of energy dissipation in the material is determined as a function of strain and strain-rate, along with a scaling relation which describes the dependence of maximum velocity on material properties. Understanding this scaling relation along with the material failure limits of the elastomer allows the prediction of material properties required for optimal performance. We demonstrate this concept experimentally by optimizing for maximum velocity in our synthetic model system, and achieve retraction velocities that exceed those in biological impulsive systems. This model system provides a foundation for future work connecting continuum performance to molecular architecture in impulsive systems.

Understanding the limits of animal models as predictors of human biology: lessons learned from the sbv IMPROVER Species Translation Challenge.

Science.gov (United States)

Rhrissorrakrai, Kahn; Belcastro, Vincenzo; Bilal, Erhan; Norel, Raquel; Poussin, Carine; Mathis, Carole; Dulize, Rémi H J; Ivanov, Nikolai V; Alexopoulos, Leonidas; Rice, J Jeremy; Peitsch, Manuel C; Stolovitzky, Gustavo; Meyer, Pablo; Hoeng, Julia

2015-02-15

Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this question cannot be addressed because it is not possible to perform experiments in humans. A reasonable alternative consists of generating responses in animal models and 'translating' those results to humans. The limitations of such translation, however, are far from clear, and systematic assessments of its actual potential are urgently needed. sbv IMPROVER (systems biology verification for Industrial Methodology for PROcess VErification in Research) was designed as a series of challenges to address translatability between humans and rodents. This collaborative crowd-sourcing initiative invited scientists from around the world to apply their own computational methodologies on a multilayer systems biology dataset composed of phosphoproteomics, transcriptomics and cytokine data derived from normal human and rat bronchial epithelial cells exposed in parallel to 52 different stimuli under identical conditions. Our aim was to understand the limits of species-to-species translatability at different levels of biological organization: signaling, transcriptional and release of secreted factors (such as cytokines). Participating teams submitted 49 different solutions across the sub-challenges, two-thirds of which were statistically significantly better than random. Additionally, similar computational methods were found to range widely in their performance within the same challenge, and no single method emerged as a clear winner across all sub-challenges. Finally, computational methods were able to effectively translate some specific stimuli and biological processes in the lung epithelial system, such as DNA synthesis, cytoskeleton and extracellular matrix, translation, immune/inflammation and growth factor/proliferation pathways, better than the expected response similarity between species. pmeyerr@us.ibm.com or Julia

Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

Science.gov (United States)

Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

2015-08-21

In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

Noninvasive biological sensor system for detection of drunk driving.

Science.gov (United States)

Murata, Kohji; Fujita, Etsunori; Kojima, Shigeyuki; Maeda, Shinitirou; Ogura, Yumi; Kamei, Tsutomu; Tsuji, Toshio; Kaneko, Shigehiko; Yoshizumi, Masao; Suzuki, Nobutaka

2011-01-01

Systems capable of monitoring the biological condition of a driver and issuing warnings during instances of drowsiness have recently been studied. Moreover, many researchers have reported that biological signals, such as brain waves, pulsation waves, and heart rate, are different between people who have and have not consumed alcohol. Currently, we are developing a noninvasive system to detect individuals driving under the influence of alcohol by measuring biological signals. We used the frequency time series analysis to attempt to distinguish between normal and intoxicated states of a person as the basis of the sensing system.

{sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

Energy Technology Data Exchange (ETDEWEB)

Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

2011-04-15

The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

Using chemistry and microfluidics to understand the spatial dynamics of complex biological networks.

Science.gov (United States)

Kastrup, Christian J; Runyon, Matthew K; Lucchetta, Elena M; Price, Jessica M; Ismagilov, Rustem F

2008-04-01

Understanding the spatial dynamics of biochemical networks is both fundamentally important for understanding life at the systems level and also has practical implications for medicine, engineering, biology, and chemistry. Studies at the level of individual reactions provide essential information about the function, interactions, and localization of individual molecular species and reactions in a network. However, analyzing the spatial dynamics of complex biochemical networks at this level is difficult. Biochemical networks are nonequilibrium systems containing dozens to hundreds of reactions with nonlinear and time-dependent interactions, and these interactions are influenced by diffusion, flow, and the relative values of state-dependent kinetic parameters. To achieve an overall understanding of the spatial dynamics of a network and the global mechanisms that drive its function, networks must be analyzed as a whole, where all of the components and influential parameters of a network are simultaneously considered. Here, we describe chemical concepts and microfluidic tools developed for network-level investigations of the spatial dynamics of these networks. Modular approaches can be used to simplify these networks by separating them into modules, and simple experimental or computational models can be created by replacing each module with a single reaction. Microfluidics can be used to implement these models as well as to analyze and perturb the complex network itself with spatial control on the micrometer scale. We also describe the application of these network-level approaches to elucidate the mechanisms governing the spatial dynamics of two networkshemostasis (blood clotting) and early patterning of the Drosophila embryo. To investigate the dynamics of the complex network of hemostasis, we simplified the network by using a modular mechanism and created a chemical model based on this mechanism by using microfluidics. Then, we used the mechanism and the model to

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

Energy Technology Data Exchange (ETDEWEB)

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host

Positioning genomics in biology education: content mapping of undergraduate biology textbooks.

Science.gov (United States)

Wernick, Naomi L B; Ndung'u, Eric; Haughton, Dominique; Ledley, Fred D

2014-12-01

Biological thought increasingly recognizes the centrality of the genome in constituting and regulating processes ranging from cellular systems to ecology and evolution. In this paper, we ask whether genomics is similarly positioned as a core concept in the instructional sequence for undergraduate biology. Using quantitative methods, we analyzed the order in which core biological concepts were introduced in textbooks for first-year general and human biology. Statistical analysis was performed using self-organizing map algorithms and conventional methods to identify clusters of terms and their relative position in the books. General biology textbooks for both majors and nonmajors introduced genome-related content after text related to cell biology and biological chemistry, but before content describing higher-order biological processes. However, human biology textbooks most often introduced genomic content near the end of the books. These results suggest that genomics is not yet positioned as a core concept in commonly used textbooks for first-year biology and raises questions about whether such textbooks, or courses based on the outline of these textbooks, provide an appropriate foundation for understanding contemporary biological science.

Set membership experimental design for biological systems

Directory of Open Access Journals (Sweden)

Marvel Skylar W

2012-03-01

Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

SEEK: a systems biology data and model management platform.

NARCIS (Netherlands)

Wolstencroft, K.J.; Owen, S.; Krebs, O.; Nguyen, Q.; Stanford, N.J.; Golebiewski, M.; Weidemann, A.; Bittkowski, M.; An, L.; Shockley, D.; Snoep, J.L.; Mueller, W.; Goble, C.

2015-01-01

Background: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems

An investigation into the population abundance distribution of mRNAs, proteins, and metabolites in biological systems.

Science.gov (United States)

Lu, Chuan; King, Ross D

2009-08-15

Distribution analysis is one of the most basic forms of statistical analysis. Thanks to improved analytical methods, accurate and extensive quantitative measurements can now be made of the mRNA, protein and metabolite from biological systems. Here, we report a large-scale analysis of the population abundance distributions of the transcriptomes, proteomes and metabolomes from varied biological systems. We compared the observed empirical distributions with a number of distributions: power law, lognormal, loglogistic, loggamma, right Pareto-lognormal (PLN) and double PLN (dPLN). The best-fit for mRNA, protein and metabolite population abundance distributions was found to be the dPLN. This distribution behaves like a lognormal distribution around the centre, and like a power law distribution in the tails. To better understand the cause of this observed distribution, we explored a simple stochastic model based on geometric Brownian motion. The distribution indicates that multiplicative effects are causally dominant in biological systems. We speculate that these effects arise from chemical reactions: the central-limit theorem then explains the central lognormal, and a number of possible mechanisms could explain the long tails: positive feedback, network topology, etc. Many of the components in the central lognormal parts of the empirical distributions are unidentified and/or have unknown function. This indicates that much more biology awaits discovery.

ChemProt: A disease chemical biology database

DEFF Research Database (Denmark)

Taboureau, Olivier; Oprea, Tudor I.

2013-01-01

The integration of chemistry, biology, and informatics to study drug actions across multiple biological targets, pathways, and biological systems is an emerging paradigm in drug discovery. Rather than reducing a complex system to simplistic models, fields such as chemogenomics and translational...... informatics are seeking to build a holistic model for a better understanding of the drug pharmacology and clinical effects. Here we will present a webserver called ChemProt that can assist, in silico, the drug actions in the context of cellular and disease networks and contribute in the field of disease...... chemical biology, drug repurposing, and off-target effects prediction....

Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

Science.gov (United States)

Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; Walhout, Albertha J. M.

2014-01-01

SUMMARY Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here we used an interspecies systems biology approach with Caenorhabditis elegans and two if its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal’s gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development and reduces fertility, but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. PMID:24529378

Invited review: gravitational biology of the neuromotor systems: a perspective to the next era

Science.gov (United States)

Edgerton, V. R.; Roy, R. R.

2000-01-01

Earth's gravity has had a significant impact on the designs of the neuromotor systems that have evolved. Early indications are that gravity also plays a key role in the ontogenesis of some of these design features. The purpose of the present review is not to assess and interpret a body of knowledge in the usual sense of a review but to look ahead, given some of the general concepts that have evolved and observations made to date, which can guide our future approach to gravitational biology. We are now approaching an era in gravitational biology during which well-controlled experiments can be conducted for sustained periods in a microgravity environment. Thus it is now possible to study in greater detail the role of gravity in phylogenesis and ontogenesis. Experiments can range from those conducted on the simplest levels of organization of the components that comprise the neuromotor system to those conducted on the whole organism. Generally, the impact of Earth's gravitational environment on living systems becomes more complex as the level of integration of the biological phenomenon of interest increases. Studies of the effects of gravitational vectors on neuromotor systems have and should continue to provide unique insight into these mechanisms that control and maintain neural control systems designed to function in Earth's gravitational environment. A number of examples are given of how a gravitational biology perspective can lead to a clearer understanding of neuromotor disorders. Furthermore, the technologies developed for spaceflight studies have contributed and should continue to contribute to studies of motor dysfunctions, such as spinal cord injury and stroke. Disorders associated with energy support and delivery systems and how these functions are altered by sedentary life styles at 1 G and by space travel in a microgravity environment are also discussed.

Tunable promoters in systems biology

DEFF Research Database (Denmark)

Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

2005-01-01

The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...

Nano- and micro-fabrication for single-molecule biological studies

NARCIS (Netherlands)

Huang, Z.

2012-01-01

Heterogeneity is a general feature in biological system. In order to avoid possible misleading effects of ensemble averaging, and to ensure a correct understanding of the biological system, it is very important to look into individuals, such as a single bio-molecule or a single cell, for details.

Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

Science.gov (United States)

Benson, Neil

2015-08-01

Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

Heavy-ion microbeam system at JAEA-Takasaki for microbeam biology

International Nuclear Information System (INIS)

Funayama, Tomoo; Wada, Seiichi; Yokota, Yuichiro

2008-01-01

Research concerning cellular responses to low dose irradiation, radiation-induced bystander effects, and the biological track structure of charged particles has recently received particular attention in the field of radiation biology. Target irradiation employing a microbeam represents a useful means of advancing this research by obviating some of the disadvantages associated with the conventional irradiation strategies. The heavy-ion microbeam system at Japan Atomic Energy Agency (JAEA)-Takasaki, which was planned in 1987 and started in the early 1990's, can provide target irradiation of heavy charged particles to biological material at atmospheric pressure using a minimum beam size 5 μm in diameter. A variety of biological material has been irradiated using this microbeam system including cultured mammalian and higher plant cells, isolated fibers of mouse skeletal muscle, silkworm (Bombyx mori) embryos and larvae, Arabidopsis thaliana roots, and the nematode Caenorhabditis elegans. The system can be applied to the investigation of mechanisms within biological organisms not only in the context of radiation biology, but also in the fields of general biology such as physiology, developmental biology and neurobiology, and should help to establish and contribute to the field of 'microbeam biology'. (author)

Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance.

Science.gov (United States)

Kalluri, Udaya C; Yin, Hengfu; Yang, Xiaohan; Davison, Brian H

2014-12-01

Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host that carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

Science.gov (United States)

Ippolito, Corey; Plice, Laura; Pisanich, Greg

2003-01-01

The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

Preparation and Characterization Challenges to Understanding Environmental and Biological Impacts of Ceria Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Karakoti, Ajay S.; Munusamy, Prabhakaran; Hostetler, Kasey E.; Kodali, Vamsi K.; Kuchibhatla, Satyanarayana V N T; Orr, Galya; Pounds, Joel G.; Teeguarden, Justin G.; Thrall, Brian D.; Baer, Donald R.

2012-08-01

It has been increasingly recognized that understanding and predicting the behaviors of nanoparticles is often limited by the degree to which the particles can be reliably produced and are adequately characterized. Examining data from the literature for ceria nanoparticles suggests that thermal history is one factor that has a strong influence on biological impact. Thermal processing may alter many physicochemical properties of the particles including density, crystal structure and the presence of surface contamination, but these may not be sufficiently recorded or reported to determine the ultimate source of an observed impact. A second example shows the types of difficulties that can be encountered in efforts to apply a well-studied synthesis route to producing well defined particles for biological studies. These examples and others highlight the importance of characterizing particles thoroughly and recording details of particle processing and history that are often not recorded and/or reported.

Systems Biology Markup Language (SBML) Level 2 Version 5: Structures and Facilities for Model Definitions.

Science.gov (United States)

Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

2015-09-04

Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org.

Systems Biology Markup Language (SBML Level 2 Version 5: Structures and Facilities for Model Definitions

Directory of Open Access Journals (Sweden)

Hucka Michael

2015-06-01

Full Text Available Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

Systems Biology Graphical Notation: Entity Relationship language Level 1 Version 2

Directory of Open Access Journals (Sweden)

Sorokin Anatoly

2015-06-01

Full Text Available The Systems Biological Graphical Notation (SBGN is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD, Entity Relationship (ER and Activity Flow (AF, allow for the representation of different aspects of biological and biochemical systems at different levels of detail.

Molecular biology and its applications in orthodontics and oral and maxillofacial surgery

NARCIS (Netherlands)

Ren, Yjin

2005-01-01

: Molecular biology is an exciting, rapidly expanding field, which has enabled enormously greater understanding of the biology of diseases and malfunctions in many fields. It chiefly concerns itself with understanding the interactions between the various systems of a cell, including the

Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Nielsen, Jens; Jewett, Michael Christopher

2008-01-01

in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

EURASIP journal on bioinformatics & systems biology

National Research Council Canada - National Science Library

2006-01-01

"The overall aim of "EURASIP Journal on Bioinformatics and Systems Biology" is to publish research results related to signal processing and bioinformatics theories and techniques relevant to a wide...

From noise to synthetic nucleoli: can synthetic biology achieve new insights?

Science.gov (United States)

Ciechonska, Marta; Grob, Alice; Isalan, Mark

2016-04-18

Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks. This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks. Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

In vivo robotics: the automation of neuroscience and other intact-system biological fields.

Science.gov (United States)

Kodandaramaiah, Suhasa B; Boyden, Edward S; Forest, Craig R

2013-12-01

Robotic and automation technologies have played a huge role in in vitro biological science, having proved critical for scientific endeavors such as genome sequencing and high-throughput screening. Robotic and automation strategies are beginning to play a greater role in in vivo and in situ sciences, especially when it comes to the difficult in vivo experiments required for understanding the neural mechanisms of behavior and disease. In this perspective, we discuss the prospects for robotics and automation to influence neuroscientific and intact-system biology fields. We discuss how robotic innovations might be created to open up new frontiers in basic and applied neuroscience and present a concrete example with our recent automation of in vivo whole-cell patch clamp electrophysiology of neurons in the living mouse brain. © 2013 New York Academy of Sciences.

Revision history aware repositories of computational models of biological systems.

Science.gov (United States)

Miller, Andrew K; Yu, Tommy; Britten, Randall; Cooling, Mike T; Lawson, James; Cowan, Dougal; Garny, Alan; Halstead, Matt D B; Hunter, Peter J; Nickerson, David P; Nunns, Geo; Wimalaratne, Sarala M; Nielsen, Poul M F

2011-01-14

Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs) for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. We have extended the Physiome Model Repository software to be fully revision history aware

Revision history aware repositories of computational models of biological systems

Directory of Open Access Journals (Sweden)

Nickerson David P

2011-01-01

Full Text Available Abstract Background Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. Results We have extended the Physiome Model

Marine biological data and information management system

Digital Repository Service at National Institute of Oceanography (India)

Sarupria, J.S.

Indian National Oceanographic Data Centre (INODC) is engaged in developing a marine biological data and information management system (BIODIMS). This system will contain the information on zooplankton in the water column, zoobenthic biomass...

The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core.

Science.gov (United States)

Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

2018-03-09

Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

Predictive modelling of complex agronomic and biological systems.

Science.gov (United States)

Keurentjes, Joost J B; Molenaar, Jaap; Zwaan, Bas J

2013-09-01

Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real-world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead. © 2013 John Wiley & Sons Ltd.

Systems Biology of the Fluxome

Directory of Open Access Journals (Sweden)

Miguel A. Aon

2015-07-01

Full Text Available The advent of high throughput -omics has made the accumulation of comprehensive data sets possible, consisting of changes in genes, transcripts, proteins and metabolites. Systems biology-inspired computational methods for translating metabolomics data into fluxomics provide a direct functional, dynamic readout of metabolic networks. When combined with appropriate experimental design, these methods deliver insightful knowledge about cellular function under diverse conditions. The use of computational models accounting for detailed kinetics and regulatory mechanisms allow us to unravel the control and regulatory properties of the fluxome under steady and time-dependent behaviors. This approach extends the analysis of complex systems from description to prediction, including control of complex dynamic behavior ranging from biological rhythms to catastrophic lethal arrhythmias. The powerful quantitative metabolomics-fluxomics approach will help our ability to engineer unicellular and multicellular organisms evolve from trial-and-error to a more predictable process, and from cells to organ and organisms.

Quantitative computational models of molecular self-assembly in systems biology.

Science.gov (United States)

Thomas, Marcus; Schwartz, Russell

2017-05-23

Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis.

Science.gov (United States)

Schubert, Thomas; Römer, Winfried

2015-11-01

Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of undergraduate students' conceptual models of a complex biological system across a diverse body of learners

Science.gov (United States)

Dirnbeck, Matthew R.

Biological systems pose a challenge both for learners and teachers because they are complex systems mediated by feedback loops; networks of cause-effect relationships; and non-linear, hierarchical, and emergent properties. Teachers and scientists routinely use models to communicate ideas about complex systems. Model-based pedagogies engage students in model construction as a means of practicing higher-order reasoning skills. One such modeling paradigm describes systems in terms of their structures, behaviors, and functions (SBF). The SBF framework is a simple modeling language that has been used to teach about complex biological systems. Here, we used student-generated SBF models to assess students' causal reasoning in the context of a novel biological problem on an exam. We compared students' performance on the modeling problem, their performance on a set of knowledge/comprehension questions, and their performance on a set of scientific reasoning questions. We found that students who performed well on knowledge and understanding questions also constructed more networked, higher quality models. Previous studies have shown that learners' mental maps increase in complexity with increased expertise. We wanted to investigate if biology students with varying levels of training in biology showed a similar pattern when constructing system models. In a pilot study, we administered the same modeling problem to two additional groups of students: 1) an animal physiology course for students pursuing a major in biology (n=37) and 2) an exercise physiology course for non-majors (n=27). We found that there was no significant difference in model organization across the three student populations, but there was a significant difference in the ability to represent function between the three populations. Between the three groups the non-majors had the lowest function scores, the introductory majors had the middle function scores, and the upper division majors had the highest function

Vibrational resonances in biological systems at microwave frequencies.

Science.gov (United States)

Adair, Robert K

2002-03-01

Many biological systems can be expected to exhibit resonance behavior involving the mechanical vibration of system elements. The natural frequencies of such resonances will, generally, be in the microwave frequency range. Some of these systems will be coupled to the electromagnetic field by the charge distributions they carry, thus admitting the possibility that microwave exposures may generate physiological effects in man and other species. However, such microwave excitable resonances are expected to be strongly damped by interaction with their aqueous biological environment. Although those dissipation mechanisms have been studied, the limitations on energy transfers that follow from the limited coupling of these resonances to the electromagnetic field have not generally been considered. We show that this coupling must generally be very small and thus the absorbed energy is so strongly limited that such resonances cannot affect biology significantly even if the systems are much less strongly damped than expected from basic dissipation models.

Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

Directory of Open Access Journals (Sweden)

Andreas F.R. Sommer

2011-07-01

Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

Materiomics: biological protein materials, from nano to macro

Science.gov (United States)

Cranford, Steven; Buehler, Markus J

2010-01-01

Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics – discovering Nature’s complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents) such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and replicate Nature’s materials have been hindered by our lack of fundamental understanding of these materials’ intricate hierarchical structures, scale-bridging mechanisms, and complex material components that bestow protein-based materials their unique properties

Has Neo-Darwinism failed clinical medicine: does systems biology have to?

Science.gov (United States)

Joyner, Michael J

2015-01-01

In this essay I argue that Neo-Darwinism ultimately led to an oversimplified genotype equals phenotype view of human disease. This view has been called into question by the unexpected results of the Human Genome Project which has painted a far more complex picture of the genetic features of human disease than was anticipated. Cell centric Systems Biology is now attempting to reconcile this complexity. However, it too is limited because most common chronic diseases have systemic components not predicted by their intracellular responses alone. In this context, congestive heart failure is a classic example of this general problem and I discuss it as a systemic disease vs. one solely related to dysfunctional cardiomyocytes. I close by arguing that a physiological perspective is essential to reconcile reductionism with what is required to understand and treat disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Complex systems of biological interest stability under ionising radiations

International Nuclear Information System (INIS)

Maclot, Sylvain

2014-01-01

This PhD work presents the study of stability of molecular systems of biological interest in the gas phase after interaction with ionising radiations. The use of ionising radiation can probe the physical chemistry of complex systems at the molecular scale and thus consider their intrinsic properties. Beyond the fundamental aspect, this work is part of the overall understanding of radiation effects on living organisms and in particular the use of ionizing radiation in radiotherapy. Specifically, this study focused on the use of low-energy multiply charged ions (tens of keV) provided by the GANIL (Caen), which includes most of the experiments presented. In addition, experiments using VUV photons were also conducted at synchrotron ELETTRA (Trieste, Italy). The bio-molecular systems studied are amino acids and nucleic acid constituents. Using an experimental crossed beams device allows interaction between biomolecules and ionising radiation leads mainly to the ionization and fragmentation of the system. The study of its relaxation dynamics is by time-of-flight mass spectrometry coupled to a coincidences measurements method. It is shown that an approach combining experiment and theory allows a detailed study of the fragmentation dynamics of complex systems. The results indicate that fragmentation is generally governed by the Coulomb repulsion but the intramolecular rearrangements involve specific relaxation mechanisms. (author) [fr

Integration of Principles of Systems Biology and Radiation Biology: Toward Development of in silico Models to Optimize IUdR-Mediated Radiosensitization of DNA Mismatch Repair Deficient (Damage Tolerant) Human Cancers

International Nuclear Information System (INIS)

Kinsella, Timothy J.; Gurkan-Cavusoglu, Evren; Du, Weinan; Loparo, Kenneth A.

2011-01-01

Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR) and ionizing radiation (IR) induced DNA base damage by DNA mismatch repair (MMR). These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP), brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR-induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitization in MMR deficient (MMR − ) “damage tolerant” human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular) and to in vivo (human tumor xenografts in athymic mice) models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR − damage tolerant cancers.

Advances in the use of biologic agents for the treatment of systemic vasculitis

Science.gov (United States)

Chung, Sharon A.; Seo, Philip

2010-01-01

Purpose of review Due to the well-known toxicities of cyclophosphamide, substantial interest exists in finding other therapies to treat primary systemic vasculitis. Biologic agents have been proposed as an alternative to cyclophosphamide for these disorders because of their recent success in treating other rheumatic diseases. This article reviews the current state-of-the-art with regards to the use of biologic agents as a treatment for systemic vasculitis. Recent findings The greatest amount of experience with these agents for the treatment of systemic vasculitis is with anti-tumor necrosis factor agents, pooled intravenous immunoglobulin, and anti-B cell therapies such as rituximab. Intravenous immunoglobulin is already a standard therapy for Kawasaki's disease, but should also be considered for the treatment of ANCA-associated vasculitis when standard therapies are either ineffective or contraindicated. Early experience with tumor necrosis factor inhibitors indicates that they may be effective for the treatment of Takayasu's arteritis, but their role in the treatment of other forms of vasculitis remains controversial. Early experience with rituximab for the treatment of several forms of vasculitis has been quite promising, but must be confirmed by ongoing randomized clinical trials. Summary Biologic agents represent the next evolution in treatment for the primary systemic vasculitides. Greater understanding of these diseases has allowed use to move further away from non-specific, highly toxic therapies towards a more directed approach. As our experience with these agents increases, they will likely form the keystone of treatment in the near future. PMID:19077713

Yeast prions: structure, biology, and prion-handling systems.

Science.gov (United States)

Wickner, Reed B; Shewmaker, Frank P; Bateman, David A; Edskes, Herman K; Gorkovskiy, Anton; Dayani, Yaron; Bezsonov, Evgeny E

2015-03-01

A prion is an infectious protein horizontally transmitting a disease or trait without a required nucleic acid. Yeast and fungal prions are nonchromosomal genes composed of protein, generally an altered form of a protein that catalyzes the same alteration of the protein. Yeast prions are thus transmitted both vertically (as genes composed of protein) and horizontally (as infectious proteins, or prions). Formation of amyloids (linear ordered β-sheet-rich protein aggregates with β-strands perpendicular to the long axis of the filament) underlies most yeast and fungal prions, and a single prion protein can have any of several distinct self-propagating amyloid forms with different biological properties (prion variants). Here we review the mechanism of faithful templating of protein conformation, the biological roles of these prions, and their interactions with cellular chaperones, the Btn2 and Cur1 aggregate-handling systems, and other cellular factors governing prion generation and propagation. Human amyloidoses include the PrP-based prion conditions and many other, more common amyloid-based diseases, several of which show prion-like features. Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses. Patients with different clinical pictures of the same amyloidosis may be the equivalent of yeasts with different prion variants. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dielectric relaxation in biological systems physical principles, methods, and applications

CERN Document Server

Feldman, Yuri

2015-01-01

This title covers the theoretical basis and practical aspects of the study of dielectric properties of biological systems, such as water, electrolyte and polyelectrolytes, solutions of biological macromolecules, cells suspensions and cellular systems.

Systems-biology dissection of eukaryotic cell growth

Directory of Open Access Journals (Sweden)

Andrews Justen

2010-05-01

Full Text Available Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68

Understanding land administration systems

DEFF Research Database (Denmark)

P. Williamson, Ian; Enemark, Stig; Wallace, Judy

2008-01-01

This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems. Readers may recall the first part of the paper in October issue of Coordinates. Here is the concluding part that focuses on the changing...

It’s the System, Stupid: How Systems Biology Is Transforming

Science.gov (United States)

2010-01-01

So far, little is known about systems biology and its potential for changing how we diagnose and treat disease. That will change soon, say the systems experts, who advise payers to begin learning now about how it could make healthcare efficient. PMID:22478806

Review and application of group theory to molecular systems biology.

Science.gov (United States)

Rietman, Edward A; Karp, Robert L; Tuszynski, Jack A

2011-06-22

In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

A dedicated database system for handling multi-level data in systems biology

OpenAIRE

Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Background Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging...

GeneLab: A Systems Biology Platform for Spaceflight Omics Data

Science.gov (United States)

Reinsch, Sigrid S.; Lai, San-Huei; Chen, Rick; Thompson, Terri; Berrios, Daniel; Fogle, Homer; Marcu, Oana; Timucin, Linda; Chakravarty, Kaushik; Coughlan, Joseph

2015-01-01

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. Resources to support large numbers of spaceflight investigations are limited. NASA's GeneLab project is maximizing the science output from these experiments by: (1) developing a unique public bioinformatics database that includes space bioscience relevant "omics" data (genomics, transcriptomics, proteomics, and metabolomics) and experimental metadata; (2) partnering with NASA-funded flight experiments through bio-sample sharing or sample augmentation to expedite omics data input to the GeneLab database; and (3) developing community-driven reference flight experiments. The first database, GeneLab Data System Version 1.0, went online in April 2015. V1.0 contains numerous flight datasets and has search and download capabilities. Version 2.0 will be released in 2016 and will link to analytic tools. In 2015 Genelab partnered with two Biological Research in Canisters experiments (BBRIC-19 and BRIC-20) which examine responses of Arabidopsis thaliana to spaceflight. GeneLab also partnered with Rodent Research-1 (RR1), the maiden flight to test the newly developed rodent habitat. GeneLab developed protocols for maxiumum yield of RNA, DNA and protein from precious RR-1 tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected. GeneLab is establishing partnerships with at least three planned flights for 2016. Organism-specific nationwide Science Definition Teams (SDTs) will define future GeneLab dedicated missions and ensure the broader scientific impact of the GeneLab missions. GeneLab ensures prompt release and open access to all high-throughput omics data from spaceflight and ground-based simulations of microgravity and radiation. Overall, GeneLab will facilitate the generation and query of parallel multi-omics data, and

Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits.

Science.gov (United States)

Watson, Emma; MacNeil, Lesley T; Ritter, Ashlyn D; Yilmaz, L Safak; Rosebrock, Adam P; Caudy, Amy A; Walhout, Albertha J M

2014-02-13

Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. Copyright © 2014 Elsevier Inc. All rights reserved.

Recent introduction of an allodapine bee into Fiji: A new model system for understanding biological invasions by pollinators.

Science.gov (United States)

Groom, Scott V C; Tuiwawa, Marika V; Stevens, Mark I; Schwarz, Michael P

2015-08-01

Morphology-based studies have suggested a very depauperate bee fauna for islands in the South West Pacific, and recent genetic studies since have indicated an even smaller endemic fauna with many bee species in this region resulting from human-aided dispersal. These introduced species have the potential to both disrupt native pollinator suites as well as augment crop pollination, but for most species the timings of introduction are unknown. We examined the distribution and nesting biology of the long-tongued bee Braunsapis puangensis that was first recorded from Fiji in 2007. This bee has now become widespread in Fiji and both its local abundance and geographical range are likely to increase dramatically. The impacts of this invasion are potentially enormous for agriculture and native ecosystems, but they also provide opportunities for understanding how social insect species adapt to new environments. We outline the major issues associated with this recent invasion and argue that a long-term monitoring study is needed. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Modeling of nonlinear biological phenomena modeled by S-systems.

Science.gov (United States)

Mansouri, Majdi M; Nounou, Hazem N; Nounou, Mohamed N; Datta, Aniruddha A

2014-03-01

A central challenge in computational modeling of biological systems is the determination of the model parameters. In such cases, estimating these variables or parameters from other easily obtained measurements can be extremely useful. For example, time-series dynamic genomic data can be used to develop models representing dynamic genetic regulatory networks, which can be used to design intervention strategies to cure major diseases and to better understand the behavior of biological systems. Unfortunately, biological measurements are usually highly infected by errors that hide the important characteristics in the data. Therefore, these noisy measurements need to be filtered to enhance their usefulness in practice. This paper addresses the problem of state and parameter estimation of biological phenomena modeled by S-systems using Bayesian approaches, where the nonlinear observed system is assumed to progress according to a probabilistic state space model. The performances of various conventional and state-of-the-art state estimation techniques are compared. These techniques include the extended Kalman filter (EKF), unscented Kalman filter (UKF), particle filter (PF), and the developed variational Bayesian filter (VBF). Specifically, two comparative studies are performed. In the first comparative study, the state variables (the enzyme CadA, the model cadBA, the cadaverine Cadav and the lysine Lys for a model of the Cad System in Escherichia coli (CSEC)) are estimated from noisy measurements of these variables, and the various estimation techniques are compared by computing the estimation root mean square error (RMSE) with respect to the noise-free data. In the second comparative study, the state variables as well as the model parameters are simultaneously estimated. In this case, in addition to comparing the performances of the various state estimation techniques, the effect of the number of estimated model parameters on the accuracy and convergence of these

Using insects to drive mobile robots - hybrid robots bridge the gap between biological and artificial systems.

Science.gov (United States)

Ando, Noriyasu; Kanzaki, Ryohei

2017-09-01

The use of mobile robots is an effective method of validating sensory-motor models of animals in a real environment. The well-identified insect sensory-motor systems have been the major targets for modeling. Furthermore, mobile robots implemented with such insect models attract engineers who aim to avail advantages from organisms. However, directly comparing the robots with real insects is still difficult, even if we successfully model the biological systems, because of the physical differences between them. We developed a hybrid robot to bridge the gap. This hybrid robot is an insect-controlled robot, in which a tethered male silkmoth (Bombyx mori) drives the robot in order to localize an odor source. This robot has the following three advantages: 1) from a biomimetic perspective, the robot enables us to evaluate the potential performance of future insect-mimetic robots; 2) from a biological perspective, the robot enables us to manipulate the closed-loop of an onboard insect for further understanding of its sensory-motor system; and 3) the robot enables comparison with insect models as a reference biological system. In this paper, we review the recent works regarding insect-controlled robots and discuss the significance for both engineering and biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Critical Perspective on Synthetic Biology

OpenAIRE

Michel Morange

2009-01-01

Synthetic biology emerged around 2000 as a new biological discipline. It shares with systems biology the same modular vision of organisms, but is more concerned with applications than with a better understanding of the functioning of organisms. A herald of this new discipline is Craig Venter who aims to create an artificial microorganism with the minimal genome compatible with life and to implement into it different 'functional modules' to generate new micro-organisms adapted to specific task...

Biological Soft Robotics.

Science.gov (United States)

Feinberg, Adam W

2015-01-01

In nature, nanometer-scale molecular motors are used to generate force within cells for diverse processes from transcription and transport to muscle contraction. This adaptability and scalability across wide temporal, spatial, and force regimes have spurred the development of biological soft robotic systems that seek to mimic and extend these capabilities. This review describes how molecular motors are hierarchically organized into larger-scale structures in order to provide a basic understanding of how these systems work in nature and the complexity and functionality we hope to replicate in biological soft robotics. These span the subcellular scale to macroscale, and this article focuses on the integration of biological components with synthetic materials, coupled with bioinspired robotic design. Key examples include nanoscale molecular motor-powered actuators, microscale bacteria-controlled devices, and macroscale muscle-powered robots that grasp, walk, and swim. Finally, the current challenges and future opportunities in the field are addressed.

Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

Science.gov (United States)

Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

2016-01-01

Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Branching processes in biology

CERN Document Server

Kimmel, Marek

2015-01-01

This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex...

From Process Understanding Via Soil Functions to Sustainable Soil Management - A Systemic Approach

Science.gov (United States)

Wollschlaeger, U.; Bartke, S.; Bartkowski, B.; Daedlow, K.; Helming, K.; Kogel-Knabner, I.; Lang, B.; Rabot, E.; Russell, D.; Stößel, B.; Weller, U.; Wiesmeier, M.; Rabot, E.; Vogel, H. J.

2017-12-01

Fertile soils are central resources for the production of biomass and the provision of food and energy. A growing world population and latest climate targets lead to an increasing demand for both, food and bio-energy, which requires preserving and improving the long-term productivity of soils as a bio-economic resource. At the same time, other soil functions and ecosystem services need to be maintained: filter for clean water, carbon sequestration, provision and recycling of nutrients, and habitat for biological activity. All these soil functions result from the interaction of a multitude of physical, chemical and biological processes that are not yet sufficiently understood. In addition, we lack understanding about the interplay between the socio-economic system and the soil system and how soil functions benefit human wellbeing. Hence, a solid and integrated assessment of soil quality requires the consideration of the ensemble of soil functions and its relation to soil management to finally be able to develop site-specific options for sustainable soil management. We present an integrated modeling approach that investigates the influence of soil management on the ensemble of soil functions. It is based on the mechanistic relationships between soil functional attributes, each explained by a network of interacting processes as derived from scientific evidence. As the evidence base required for feeding the model is for the most part stored in the existing scientific literature, another central component of our work is to set up a public "knowledge-portal" providing the infrastructure for a community effort towards a comprehensive knowledge base on soil processes as a basis for model developments. The connection to the socio-economic system is established using the Drivers-Pressures-Impacts-States-Responses (DPSIR) framework where our improved understanding about soil ecosystem processes is linked to ecosystem services and resource efficiency via the soil functions.

Systems Biology Graphical Notation: Entity Relationship language Level 1 Version 2.

Science.gov (United States)

Sorokin, Anatoly; Le Novère, Nicolas; Luna, Augustin; Czauderna, Tobias; Demir, Emek; Haw, Robin; Mi, Huaiyu; Moodie, Stuart; Schreiber, Falk; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Entity Relationship language (ER) represents biological entities and their interactions and relationships within a network. SBGN ER focuses on all potential relationships between entities without considering temporal aspects. The nodes (elements) describe biological entities, such as proteins and complexes. The edges (connections) provide descriptions of interactions and relationships (or influences), e.g., complex formation, stimulation and inhibition. Among all three languages of SBGN, ER is the closest to protein interaction networks in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

Biological Principles and Threshold Concepts for Understanding Natural Selection. Implications for Developing Visualizations as a Pedagogic Tool

Science.gov (United States)

Tibell, Lena A. E.; Harms, Ute

2017-11-01

Modern evolutionary theory is both a central theory and an integrative framework of the life sciences. This is reflected in the common references to evolution in modern science education curricula and contexts. In fact, evolution is a core idea that is supposed to support biology learning by facilitating the organization of relevant knowledge. In addition, evolution can function as a pivotal link between concepts and highlight similarities in the complexity of biological concepts. However, empirical studies in many countries have for decades identified deficiencies in students' scientific understanding of evolution mainly focusing on natural selection. Clearly, there are major obstacles to learning natural selection, and we argue that to overcome them, it is essential to address explicitly the general abstract concepts that underlie the biological processes, e.g., randomness or probability. Hence, we propose a two-dimensional framework for analyzing and structuring teaching of natural selection. The first—purely biological—dimension embraces the three main principles variation, heredity, and selection structured in nine key concepts that form the core idea of natural selection. The second dimension encompasses four so-called thresholds, i.e., general abstract and/or non-perceptual concepts: randomness, probability, spatial scales, and temporal scales. We claim that both of these dimensions must be continuously considered, in tandem, when teaching evolution in order to allow development of a meaningful understanding of the process. Further, we suggest that making the thresholds tangible with the aid of appropriate kinds of visualizations will facilitate grasping of the threshold concepts, and thus, help learners to overcome the difficulties in understanding the central theory of life.

PathSys: integrating molecular interaction graphs for systems biology

Directory of Open Access Journals (Sweden)

Raval Alpan

2006-02-01

Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

Echinococcus as a model system: biology and epidemiology.

Science.gov (United States)

Thompson, R C A; Jenkins, D J

2014-10-15

The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearing areas of the country inflicted a serious medical and economic burden on the country. This resulted in an investment in both basic and applied research aimed at learning more about the biology and life cycle of Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmental biology and ecology, and the value of Echinococcus as a model system in a broad range of research, from fundamental biology to theoretical control systems. These studies formed the foundation for an international, diverse and ongoing research effort on the hydatid organisms encompassing stem cell biology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. We describe the development, nature and diversity of this research, and how it was initiated in Australia but subsequently has stimulated much international and collaborative research on Echinococcus. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The relativity of biological function.

Science.gov (United States)

Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

2015-12-01

Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.

Native American Students' Understanding of Geologic Time Scale: 4th-8th Grade Ojibwe Students' Understanding of Earth's Geologic History

Science.gov (United States)

Nam, Younkyeong; Karahan, Engin; Roehrig, Gillian

2016-01-01

Geologic time scale is a very important concept for understanding long-term earth system events such as climate change. This study examines forty-three 4th-8th grade Native American--particularly Ojibwe tribe--students' understanding of relative ordering and absolute time of Earth's significant geological and biological events. This study also…

The Coastal Ocean Prediction Systems program: Understanding and managing our coastal ocean

International Nuclear Information System (INIS)

Eden, H.F.; Mooers, C.N.K.

1990-06-01

The goal of COPS is to couple a program of regular observations to numerical models, through techniques of data assimilation, in order to provide a predictive capability for the US coastal ocean including the Great Lakes, estuaries, and the entire Exclusive Economic Zone (EEZ). The objectives of the program include: determining the predictability of the coastal ocean and the processes that govern the predictability; developing efficient prediction systems for the coastal ocean based on the assimilation of real-time observations into numerical models; and coupling the predictive systems for the physical behavior of the coastal ocean to predictive systems for biological, chemical, and geological processes to achieve an interdisciplinary capability. COPS will provide the basis for effective monitoring and prediction of coastal ocean conditions by optimizing the use of increased scientific understanding, improved observations, advanced computer models, and computer graphics to make the best possible estimates of sea level, currents, temperatures, salinities, and other properties of entire coastal regions

Biological effects of particles from the paris subway system.

Science.gov (United States)

Bachoual, Rafik; Boczkowski, Jorge; Goven, Delphine; Amara, Nadia; Tabet, Lyes; On, Dinhill; Leçon-Malas, Véronique; Aubier, Michel; Lanone, Sophie

2007-10-01

Paris subway system has transient biological effects. Further studies are needed to better understand the pathophysiological implications of these findings.

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.

Science.gov (United States)

Pârvu, Ovidiu; Gilbert, David

2016-01-01

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour

Anion binding in biological systems

Energy Technology Data Exchange (ETDEWEB)

Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

2009-11-15

We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

Anion binding in biological systems

International Nuclear Information System (INIS)

Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

2009-01-01

We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L 3 (2p 3/2 ) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

Anion binding in biological systems

Science.gov (United States)

Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

2009-11-01

We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 2 Core

Directory of Open Access Journals (Sweden)

Hucka Michael

2018-03-01

Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 1 Core

Directory of Open Access Journals (Sweden)

Hucka Michael

2018-04-01

Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Release 2 of Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. No design changes have been made to the description of models between Release 1 and Release 2; changes are restricted to the format of annotations, the correction of errata and the addition of clarifications. Other materials and software are available from the SBML project website at http://sbml.org/.

Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

Science.gov (United States)

Yang, Laurence; Tan, Justin; O'Brien, Edward J; Monk, Jonathan M; Kim, Donghyuk; Li, Howard J; Charusanti, Pep; Ebrahim, Ali; Lloyd, Colton J; Yurkovich, James T; Du, Bin; Dräger, Andreas; Thomas, Alex; Sun, Yuekai; Saunders, Michael A; Palsson, Bernhard O

2015-08-25

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2

Directory of Open Access Journals (Sweden)

Mi Huaiyu

2015-06-01

Full Text Available The Systems Biological Graphical Notation (SBGN is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD, Entity Relationship (ER and Activity Flow (AF, allow for the representation of different aspects of biological and biochemical systems at different levels of detail.

The Virtual Liver Network: systems understanding from bench to bedside.

Science.gov (United States)

Henney, Adriano; Coaker, Hannah

2014-01-01

Adriano Henney speaks to Hannah Coaker, Commissioning Editor. After achieving a PhD in medicine and spending many years in academic research in the field of cardiovascular disease, Adriano Henney was recruited by Zeneca Pharmaceuticals from a British Heart Foundation Senior Fellowship, where he led the exploration of new therapeutic approaches in atherosclerosis, specifically focusing on his research interests in vascular biology. Following the merger with Astra to form AstraZeneca, Henney became responsible for exploring strategic improvements to the company's approaches to pharmaceutical target identification and the reduction of attrition in early development, directing projects across research sites and across functional project teams in the USA, Sweden and the UK. This resulted in the creation of a new multidisciplinary department that focused on pathway mapping, modeling and simulation and supporting projects across research and development, which evolved into the establishment of the practice of systems biology within the company. Here, projects prototyped the application of mechanistic disease-modeling approaches in order to support the discovery of innovative new medicines, such as Iressa®. Since leaving AstraZeneca, Henney has continued his interest in systems biology, synthetic biology and systems medicine through his company, Obsidian Biomedical Consulting Ltd. He now directs a major €50 million German national flagship program – the Virtual Liver Network – which is currently the largest systems biology program in Europe.

Target recognition and scene interpretation in image/video understanding systems based on network-symbolic models

Science.gov (United States)

Kuvich, Gary

2004-08-01

Vision is only a part of a system that converts visual information into knowledge structures. These structures drive the vision process, resolving ambiguity and uncertainty via feedback, and provide image understanding, which is an interpretation of visual information in terms of these knowledge models. These mechanisms provide a reliable recognition if the object is occluded or cannot be recognized as a whole. It is hard to split the entire system apart, and reliable solutions to the target recognition problems are possible only within the solution of a more generic Image Understanding Problem. Brain reduces informational and computational complexities, using implicit symbolic coding of features, hierarchical compression, and selective processing of visual information. Biologically inspired Network-Symbolic representation, where both systematic structural/logical methods and neural/statistical methods are parts of a single mechanism, is the most feasible for such models. It converts visual information into relational Network-Symbolic structures, avoiding artificial precise computations of 3-dimensional models. Network-Symbolic Transformations derive abstract structures, which allows for invariant recognition of an object as exemplar of a class. Active vision helps creating consistent models. Attention, separation of figure from ground and perceptual grouping are special kinds of network-symbolic transformations. Such Image/Video Understanding Systems will be reliably recognizing targets.

The molecular biology of prostate cancer: current understanding and clinical implications.

Science.gov (United States)

Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

2018-04-01

With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the

Applications of dynamical systems in biology and medicine

CERN Document Server

Radunskaya, Ami

2015-01-01

This volume highlights problems from a range of biological and medical applications that can be interpreted as questions about system behavior or control.  Topics include drug resistance in cancer and malaria, biological fluid dynamics, auto-regulation in the kidney, anti-coagulation therapy, evolutionary diversification and photo-transduction.  Mathematical techniques used to describe and investigate these biological and medical problems include ordinary, partial and stochastic differentiation equations, hybrid discrete-continuous approaches, as well as 2 and 3D numerical simulation. .

Thai in-service teacher understanding of nature of science in biology teaching: Case of Mali

Science.gov (United States)

Aiemsum-ang, Napapan; Yuenyong, Chokchai

2018-01-01

This paper aimed to investigate the existing ideas of nature of science (NOS) teaching in Thailand biology classroom. The study reported the existing ideas of nature of science (NOS) teaching of one biology teacher Mrs. Mali who had been teaching for 6 years at in a school in Khon Kaen city. Methodology regarded interpretive paradigm. Tools of interpretation included 2 months of classroom observation, interviewing, and questionnaire of NOS. The findings revealed Mali held good understanding of the nature of science in the aspect of the use of evidence, the aspect of knowledge inquiry through different observation and deduction, the aspect of creativity and imagination influencing science knowledge inquiry, and the aspect of changeable scientific knowledge. Her biology teaching indicated that she used both the deficient nature of science approach and the implicit nature of science approach. The implicit nature of science approach was applied mostly in 7 periods and only 2 periods were arranged using the deficient nature of science approach. The paper has implication for professional development and pre-service program on NOS teaching in Thailand.

Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach.

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Ida Autiero

Full Text Available BACKGROUND: A microorganism is a complex biological system able to preserve its functional features against external perturbations and the ability of the living systems to oppose to these external perturbations is defined "robustness". The antibiotic resistance, developed by different bacteria strains, is a clear example of robustness and of ability of the bacterial system to acquire a particular functional behaviour in response to environmental changes. In this work we have modeled the whole mechanism essential to the methicillin-resistance through a systems biology approach. The methicillin is a beta-lactamic antibiotic that act by inhibiting the penicillin-binding proteins (PBPs. These PBPs are involved in the synthesis of peptidoglycans, essential mesh-like polymers that surround cellular enzymes and are crucial for the bacterium survival. METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created using CellDesigner program and the data of molecular interactions are stored in Systems Biology Markup Language (SBML. To simulate the dynamic behaviour of this biochemical network, the kinetic equations were associated with each reaction. CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by methicillin, as well as the expression of PBP2a isoform, the regulation of the SCCmec elements (SCC: staphylococcal cassette chromosome and the synthesis of peptidoglycan by PBP2a. The obtained results by our integrated approach show that the model describes correctly the whole phenomenon of the methicillin resistance and is able to respond to the external perturbations in the same way of the real cell. Therefore, this model can be useful to develop new therapeutic approaches for the methicillin control and to understand the general mechanism regarding the cellular resistance to some antibiotics.

Mutagenic potential scale developed for relative evaluation of biological system response to environments presenting different gamma exposure rates

International Nuclear Information System (INIS)

Nouailhetas, Yannick; Almeida, Carlos E. Bonacossa de; Mezrahi, Arnaldo; Shu, Jane; Xavier, Ana Maria

1999-01-01

The elaboration of a mutagenic potential scale (MPS) will be accomplished through the evaluation of the frequency of induced mutations in a plant biological system in different sites. The selection of these sites will be based on general public perception of risk to health. In this selection, it will include areas such ecological paradises and also neighborhoods of nuclear reactors and uranium mining and milling industry with potential radiological impact. The developed project foresees the contribution of other research groups that will also provide data from different sites. The referred scale will be built based on the response of the genetic system that gives color to the cells of Tradescantia (BNL 4430) stamen hair to mutagenic agents. Methodological improvements has been developed aiming the computerization of mutagenic events evaluation and statistical analysis of data that will significantly increase the efficiency of the system and obtention of results. Other biological systems of environmental quality are being added to the project, for future use. MPS should facilitate the general public and professionals of the nuclear area to understand risks, on a biological basis, of exposure from radiologically impacted environments. (author)

Human Development V: Biochemistry Unable to Explain the Emergence of Biological Form (Morphogenesis and Therefore a New Principle as Source of Biological Information is Needed

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Søren Ventegodt

2006-01-01

Full Text Available Today's biomedicine builds on the conviction that biochemistry can explain the creation of the body, its anatomy and physiology. Unfortunately there are still deep mysteries strangely “fighting back” when we try to define and understand the organism and its creation in the ontogenesis as emerging from biochemistry. In analysing this from a theoretical perspective using a mathematical model focusing on the noise in complex chemical systems we argue that evolving biological structure cannot in principle be a product of chemistry. In this paper we go through the chemical gradient model and argue that this is not able to explain the ontogenesis. We discuss the used gradients as information carriers in chemical self-organizing systems and argue that by use of the “Turing structures” we are only able to modelling the mostly simple biological systems. The bio-chemical model is only able to model simple organization but not to explain the complexity of biological phenomena. We conclude that we seemingly have presented a formal proof (a NO-GO theorem that the self-organizing chemical systems that are using chemical gradients are not able to explain complex biological matters as the ontogenesis. We need a fundamentally new, information-carrying principle to understand biological information and biological order.

Programming with models: modularity and abstraction provide powerful capabilities for systems biology.

Science.gov (United States)

Mallavarapu, Aneil; Thomson, Matthew; Ullian, Benjamin; Gunawardena, Jeremy

2009-03-06

Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously.

Radiological/biological/aerosol removal system

Science.gov (United States)

Haslam, Jeffery J

2015-03-17

An air filter replacement system for existing buildings, vehicles, arenas, and other enclosed airspaces includes a replacement air filter for replacing a standard air filter. The replacement air filter has dimensions and air flow specifications that allow it to replace the standard air filter. The replacement air filter includes a filter material that removes radiological or biological or aerosol particles.

Specifications of Standards in Systems and Synthetic Biology.

Science.gov (United States)

Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

2015-09-04

Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

The Role of Soil Biological Function in Regulating Agroecosystem Services and Sustainability in the Quesungual Agroforestry System

Science.gov (United States)

Fonte, S.; Pauli, N.; Rousseau, L.; SIX, J. W. U. A.; Barrios, E.

2014-12-01

The Quesungual agroforestry system from western Honduras has been increasingly promoted as a promising alternative to traditional slash-and-burn agriculture in tropical dry forest regions of the Americas. Improved residue management and the lack of burning in this system can greatly impact soil biological functioning and a number of key soil-based ecosystem services, yet our understanding of these processes has not been thoroughly integrated to understand system functionality as a whole that can guide improved management. To address this gap, we present a synthesis of various field studies conducted in Central America aimed at: 1) quantifying the influence of the Quesungual agroforestry practices on soil macrofauna abundance and diversity, and 2) understanding how these organisms influence key soil-based ecosystem services that ultimately drive the success of this system. A first set of studies examined the impact of agroecosystem management on soil macrofauna populations, soil fertility and key soil processes. Results suggest that residue inputs (derived from tree biomass pruning), a lack of burning, and high tree densities, lead to conditions that support abundant, diverse soil macrofauna communities under agroforestry, with soil organic carbon content comparable to adjacent forest. Additionally, there is great potential in working with farmers to develop refined soil quality indicators for improved land management. A second line of research explored interactions between residue management and earthworms in the regulation of soil-based ecosystem services. Earthworms are the most prominent ecosystem engineers in these soils. We found that earthworms are key drivers of soil structure maintenance and the stabilization of soil organic matter within soil aggregates, and also had notable impacts on soil nutrient dynamics. However, the impact of earthworms appears to depend on residue management practices, thus indicating the need for an integrated approach for

The effects of academic literacy instruction on engagement and conceptual understanding of biology of ninth-grade students

Science.gov (United States)

Larson, Susan C.

Academic language, discourse, vocabulary, motivation, and comprehension of complex texts and concepts are keys to learning subject-area content. The need for a disciplinary literacy approach in high school classrooms accelerates as students become increasing disengaged in school and as content complexity increases. In the present quasi-experimental mixed-method study, a ninth-grade biology unit was designed with an emphasis on promoting academic literacy skills, discourse, meaningful constructivist learning, interest development, and positive learning experiences in order to learn science content. Quantitative and qualitative analyses on a variety of measures completed by 222 students in two high schools revealed that those who received academic literacy instruction in science class performed at significantly higher levels of conceptual understanding of biology content, academic language and vocabulary use, reasoned thought, engagement, and quality of learning experience than control-group students receiving traditionally-organized instruction. Academic literacy was embedded into biology instruction to engage students in meaning-making discourses of science to promote learning. Academic literacy activities were organized according the phases of interest development to trigger and sustain interest and goal-oriented engagement throughout the unit. Specific methods included the Generative Vocabulary Matrix (GVM), scenario-based writing, and involvement in a variety of strategically-placed discourse activities to sustain or "boost" engagement for learning. Traditional instruction for the control group included teacher lecture, whole-group discussion, a conceptual organizer, and textbook reading. Theoretical foundations include flow theory, sociocultural learning theory, and interest theory. Qualitative data were obtained from field notes and participants' journals. Quantitative survey data were collected and analyzed using the Experience Sampling Method (ESM) to

Materiomics: biological protein materials, from nano to macro

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Steven Cranford

2010-11-01

Full Text Available Steven Cranford, Markus J BuehlerCenter for Materials Science and Engineering, Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USAAbstract: Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics – discovering Nature’s complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and

Network science of biological systems at different scales: A review

Science.gov (United States)

Gosak, Marko; Markovič, Rene; Dolenšek, Jurij; Slak Rupnik, Marjan; Marhl, Marko; Stožer, Andraž; Perc, Matjaž

2018-03-01

Network science is today established as a backbone for description of structure and function of various physical, chemical, biological, technological, and social systems. Here we review recent advances in the study of complex biological systems that were inspired and enabled by methods of network science. First, we present

Quantitative, high-resolution proteomics for data-driven systems biology

DEFF Research Database (Denmark)

Cox, J.; Mann, M.

2011-01-01

Systems biology requires comprehensive data at all molecular levels. Mass spectrometry (MS)-based proteomics has emerged as a powerful and universal method for the global measurement of proteins. In the most widespread format, it uses liquid chromatography (LC) coupled to high-resolution tandem...... primary structure of proteins including posttranslational modifications, to localize proteins to organelles, and to determine protein interactions. Here, we describe the principles of analysis and the areas of biology where proteomics can make unique contributions. The large-scale nature of proteomics...... data and its high accuracy pose special opportunities as well as challenges in systems biology that have been largely untapped so far....

Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.