Systems biology

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Systems biology is the study of the interactions between the components of a biological system, and how these interactions give rise to the function and behaviour of that system (for example, the enzymes and metabolites in a metabolic pathway)<ref name = "defandperspectives">Snoep J.L. and Westerhoff H.V.; Alberghina L. and Westerhoff H.V. (Eds.) (2005.). "From isolation to integration, a systems biology approach for building the Silicon Cell". Systems Biology: Definitions and Perspectives, p7, Springer-Verlag.</ref><ref name = "isbdef">Systems Biology - the 21st Century Science.</ref>.

The systems biology approach often involves the development of mechanistic models, such as the reconstruction of dynamic systems from the quantitative properties of their elementary building blocks. For instance, a cellular network can be modelled mathematically using methods coming from chemical kinetics and control theory. Due to the large number of parameters, variables and constraints in cellular networks, numerical and computational techniques are often used. Other aspects of computer science are also used in systems biology, including text mining to find parameter data from literature, online databases and repositories for sharing data and models (such as BioModels Database), and the development of the Systems Biology Markup Language.

The systems biology approach is characterised by a cycle of theory, computational modelling and experiment to quantatively describe cells or cell processes<ref name="bbsrc">Systems Biology: Modelling, Simulation and Experimental Validation.</ref><ref name="quant">Kholodenko B.N., Bruggeman F.J., Sauro H.M.; Alberghina L. and Westerhoff H.V.(Eds.) (2005.). "Mechanistic and modular approaches to modeling and inference of cellular regulatory networks". Systems Biology: Definitions and Perspectives, p143, Springer-Verlag.</ref>. Since the objective is a model of all the interactions in a system, the experimental techniques that most suit systems biology are those that are system-wide and attempt to be as complete as possible. Therefore, transcriptomics, metabolomics, proteomics and high-throughput techniques are used to collect quantitative data for the construction and validation of models.

1 History
2 Techniques used in systems biology
3 Applications
4 Systems biology research centres
5 Systems biology organizations and communities
6 Bibliography
- 6.1 Books
- 6.2 Articles
7 External links
8 See also
9 References

[edit] History

Systems Biology finds its roots in quantitative modelling of enzyme kinetics, a discipline that flourished between 1900 and 1970, but also in the simulations developed to study neurophysiology, and the control theory, or cybernetics. One of the theoreticists who can be seen as a precusor of systems biology is Ludwig von Bertalanffy with his general systems theory. In 1952, the British neurophysiologists and nobel prize winners Alan Lloyd Hodgkin and Andrew Fielding Huxley constructed a mathematical model explaining the action potential propagating along the axon of a neuronal cell. In 1960, Denis Noble developed the first computer model of a beating heart. The years 60s and 70s view the development of several approaches to study complex molecular systems, such as the Metabolic Control Analysis. The successes of molecular biology throughout the 80s, coupled with a scepticism toward theoretical biology, that then promised more than it achieved, caused the quantitative modelling of biological processes to become a somehow minor field. However the birth of functional genomics in the 90s meant that large quantity of good quality data became available, while the computing power exploded, making possible more realistic models. In 1997, the group of Masaru Tomita published the first quantitative model of the metabolism of a whole cell. Around the year 2000, when Institute of Systems Biology were established in Seattle and Tokyo, Systems Biology emerged as a movement in its own right, spurred on by the completion of various genome projects, the large increase in data from the omics (e.g. genomics and proteomics) and the accompanying advances in high-throughput experiments and bioinformatics. Since then, various research institutes dedicated to systems biology have been developed. As of summer 2006, due to a shortage of people in systems biology<ref name="careers">Working the Systems.</ref> several doctoral training centres in systems biology have been established in many parts of the world.

[edit] Techniques used in systems biology

The defining feature of System Biology is the ability to obtain, integrate and analyze complex data from multiple experimental sources using interdiciplinary tools. Some typical technology platforms are:

Gene expression measurement through DNA microarrays and SAGE
Protein levels through two-dimensional gel electrophoresis and mass spectrometry, including phosphoproteomics and other methods to detect chemically modified proteins.
metabolomics for small-molecule metabolites
glycomics for sugars
interactomics for interactomes

The investigations are frequently combined with large scale perturbation methods, including gene-based (RNAi, misexpression of wild type and mutant genes) and chemical approaches using small molecule libraries. Robots and automated sensors enable such large-scale experimentation and data acquisition. These technologies are still emerging and many face problems that the larger the quantity of data produced, the lower the quality. A wide variety of quantitative scientists (computational biologists, statisticians, mathematicians, computer scientists, engineers, and physicists) are working to improve the quality of these approaches and to create, refine, and retest the models to accurately reflect observations.

The investigations of a single level of biological organization (such as those listed above) are usually referred to as Systematic Systems Biology. Other areas of Systems Biology includes Integrative Systems Biology, which seeks to integrate different types of information to advance the understanding the biological whole, and Dynamic Systems Biology, which aims to uncover how the biological whole changes over time (during evolution, for example, the onset of disease or in response to a perturbation). Functional Genomics may also be considered a sub-field of Systems Biology.

[edit] Applications

Many predictions concerning the impact of genomics on health care have been proposed. For example, the development of novel therapeutics and the introduction of personalised treatments are conjectured and may become reality as a small number of biotechnology companies are using this cell-biology driven approach to the development of therapeutics. However, these predictions rely upon our ability to understand and quantify the roles that specific genes possess in the context of human and pathogen physiologies. The ultimate goal of systems biology is to derive the prerequisite knowledge and tools.

[edit] Systems biology research centres

A growing number of organizations have been created to further the study of systems biology. Some notable national systems biology centres include:

Japan: The Systems Biology Institute

Canada: The Institute for Biocomplexity and Informatics at the University of Calgary; The Ottawa Institute of Systems Biology; University of Toronto's The Center for Cellular and Biomolecular Research and Department of Cellular and Systems Biology;

United States:' The Institute for Systems Biology (ISB); the BioX program at Stanford University; the Department of Systems Biology at Harvard Medical School; the Department of Bioengineering at the University of California, San Diego; the Department of Systems Biology and Translational Medicine at the Texas A&M Health Science Center College of Medicine; the Systems Biology Research Group at the Pacific Northwest National Laboratory; the New England Complex Systems Institute, and the Center for the Study of Biological Complexity.

Italy: The Microsoft Research - University of Trento Centre for Computational and Systems Biology

United Kingdom: Systems Biology Centre at the University of Warwick, Manchester Centre for Integrative Systems Biology, Centre for Integrative Systems Biology at Imperial College, Centre for Systems Biology at Edinburgh, European Bioinformatics Institute (although not entirely devoted to systems biology, the institute comprises several groups involved such as Nicolas Le Novère's (BioModels Database), Ewan Birney's (Reactome), Nicholas Luscombe's etc)

Swizerland: Institute for Molecular Systems Biology and SystemsX

Ireland: Systems Biology Ireland

France:' laboratory of mitochondrial physiopathology, University of Bordeaux ; Helix project - INRIA.

[edit] Systems biology organizations and communities

The International Society for Systems Biology; an international society aiming at advancing systems biology research world-wide by providing a forum of scientific discussions and various academic services. Organizer of the International Conference on Systems Biology (ICSB)
The Canadian Society for Systems Biology; the world's first national organization aiming to develop and facilitate systems biology research across scientific boundaries
The Yeast Systems Biology Network; an initiative aming to link various international research groups working on yeast
International E. Coli Alliance; an initiative linking to link various research groups working on bacteria
HepatoSys; a German initiavitve focusing on endocytosis, detoxification and regeneration in human hepatocytes

[edit] Bibliography

[edit] Books

H Kitano (editor). Foundations of Systems Biology. MIT Press: 2001. ISBN 0-262-11266-3
G Bock and JA Goode (eds).In Silico" Simulation of Biological Processes, Novartis Foundation Symposium 247. John Wiley & Sons: 2002. ISBN 0-470-84480-9
E Klipp, R Herwig, A Kowald, C Wierling, and H Lehrach. Systems Biology in Practice. Wiley-VCH: 2005. ISBN 3-527-31078-9
A Kriete, R Eils. Computational Systems Biology., Elsevier - Academic Press: 2005. ISBN 012088786X
B Palsson. Systems Biology - Properties of Reconstructed Networks. Cambridge University Press: 2006. ISBN 9780521859035
U Alon. An Introduction to Systems Biology: Design Principles of Biological Circuits. CRC Press: 2006. ISBN 1584886420 is an excellent book although it has emphasis on Network Biolofy

[edit] Articles

Tomita M, Hashimoto K, Takahashi K, Shimizu T, Matsuzaki Y, Miyoshi F, Saito K, Tanida S, Yugi K, Venter JC, Hutchison CA. E-CELL: Software Environment for Whole Cell Simulation. Genome Inform Ser Workshop Genome Inform. 1997;8:147-155.

Marc Facciotti, Richard Bonneau, Leroy Hood and Nitin Baliga. Current Genomics 2004 Systems Biology Experimental Design - Considerations for Building Predictive Gene Regulatory Network Models for Prokaryotic Systems

Marc Vidal and Eileen E. M. Furlong. Nature Reviews Genetics 2004 From OMICS to systems biology

Werner, E., "The Future and Limits of Systems Biology", Science STKE 2005, pe16 (2005).

ScienceMag.org - Special Issue: Systems Biology, Science, Vol 295, No 5560, March 1, 2002
Systems Biology: An Overview - a review from the Science Creative Quarterly
Guardian.co.uk - 'The unselfish gene: The new biology is reasserting the primacy of the whole organism - the individual - over the behaviour of isolated genes', Johnjoe McFadden, The Guardian (May 6, 2005)
[1] Assessment of International Research and Development in Systems Biology (2005)