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Systems biology

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Systems biology is an academic field that seeks to integrate different levels of information to understand how biological systems function. By studying the relationships and interactions between various parts of a biological system (e.g., gene and protein networks involved in cell signaling, metabolic pathways, organelles, cells, physiological systems, organisms, etc.) it is hoped that eventually an understandable model of the whole system can be developed. Since the mathematical and analytical foundation of systems biology is far from being perfect, computer simulation and heuristics are often used as research methods.

History

The British neurophysiologists and nobel prize winners Alan Lloyd Hodgkin and Andrew Fielding Huxley pioneered the field of systems biology by introducing a mathematical model of the nerve cell in 1952. In 1960, Denis Noble caused a stir with the first computer model of a beating heart. The breakthrough of the new science came around 2000 with the completion of various genome projects with their billions of data opening the perspective to explain the totality of cellular functions.

Many of the concepts of systems biology are not new. Biologists and biochemists have long known that the detailed (reductionist) study of individual proteins is just the first step toward an understanding of the overall (integrated) life process. The current advances in biology (coming from bioinformatics in the post genomic era) are a direct result of the success of this reductionist approach.

The available experimental procedures necessarily forced a 'one protein at a time' analysis during the middle of the 20th century. Advances in experimental methodology (high-throughput screening technologies) have made the 'global' view accessible for the first time, allowing scientific research at the overall level of the cell or the organism possible.

The point is: while biologists have always known a protein must function within the context of the whole cell, it has only recently become possible to obtain data about this functional level.

Approach

In contrast to much of molecular biology, systems biology does not seek to break down a system into all of its parts and study one part of the process at a time, with the hope of being able to reassemble all the parts into a whole. Some systems biologists argue that this reductionist approach to biology must always fail, either because of nature's redundancy and complexity, or because we have not understood all the parts of the processes. Some traditionalists respond that the alleged dichotomy between holistic and reductionist approaches generally exists in the mind of observers, rather than practitioners, of science. Still others accuse systems biologists of setting vague and poorly articulated goals without proposing concrete strategies, while the projects that they actually end up working on fall so far short of the initial goals as to be reductionist according to system's biology's own terms, or simply insignificant.

There are two major and complimentary focuses in systems biology:

  • Quantitative Systems Biology - otherwise known as "systems biology measurement", it focuses on measuring and monitoring biological systems on the system level.
  • Systems Biology Modeling - focuses on mapping, explaining and predicting systemic biological processes and events through the building of computational and visualization models.

Quantitative systems biology

This subfield is concerned with quantifying molecular reponses in a biological system to a given perturbation.

Some typical technology platforms are:

New approaches are being developed by quantitative scientists (computational biologists, statisticians, mathematicians, computer scientists, engineers, and physicists) to improve our ability to make these measurements and create, refine, and retest the models until the predicted behavior accurately reflects the phenotype seen.

Systems biology modeling

Using knowledge from molecular biology, the systems biologist can causally model the biological system of interest and propose hypotheses that explain a system's behavior. These hypotheses can then be confirmed and be used as a basis for mathematically model the system. The difference between the two modeling approaches is that causal models are used to explain the effects of a biological perterbations while mathematical models are used to predict how different perterbations in the system's environment affect the system.

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. Even with today's resources and expertise, this goal is immeasurably distant.

Systems biology people and places

A large number of organizations have been created to further the study of systems biology. Of note in the United States include the Institute for Systems Biology (ISB), the BioX at Stanford University, theDepartment of Systems Biology at Harvard Medical School, the Systems Biology Research Group at the Pacific Northwest National Laboratory], and the Center for the Study of Biological Complexity. The ISB is headed by Lee Hood and is a non-profit research institute with a goal to identify strategies for predicting and preventing diseases such as cancer, diabetes and AIDS. Work at PNNL is focused on a variety of research areas, including oxidative stress and radiation, cell signaling networks, and microbial communities. Internationally, some notable systems biology organizations include Japan's Systems Biology Institute headed by Hiroaki Kitano; UK's Biosystems Informatics Institute; Canada's Ottawa Institute of Systems Biology; Swizerland's Institute for Molecular Systems Biology and SystemsX, Ireland's Systems Biology Ireland, and Russia's Institute for Systems Biology.

Systems biology societies and projects

Independent systems biology research centers

Systems biology research groups

Systems biology researchers

Systems biology companies

International conferences


Tools for systems biology

Bibliography

Books

  • H Kitano (editor). Foundations of Systems Biology. MIT Press: 2001. ISBN 0262112663
  • 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 3527310789
  • B Palsson. Systems Biology - Properties of Reconstructed Networks. Cambridge University Press: 2006. ISBN 9780521859035

Articles

  • 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
  • Nature - Molecular Systems Biology
  • 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)

See also

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