Systems biology

The Systems Biology ( synonym: Systeomik, English systems biology, integrative biology or predictive biology ) is a branch of biological science that attempts to understand biological organisms in their entirety. The goal is an integrated picture of the regulatory processes at all levels, from the genome to the proteome to the organelles up to the behavior and biomechanics of the entire organism to get. Major methods for this purpose come from systems theory and its subjects. Since, however, is not perfect, the mathematical- analytical side of systems biology, suitable research methods, often computer simulations and heuristics used. Systems biology performs the time as a major factor again in the molecular biology, which reflect on the exact timing of responses so far rather avoided, in contrast to biochemistry. Systems biology returns to the biochemical point of view the world is thinking about processes and how these change over time, but with a radical expansion of the scale. In systems biology, thousands reactants are observed, which systems biology in a much more dynamic view of biology as the results of classical molecular biology or genetics.

  • 9.1 German
  • 9.2 English

Definitions

  • Systems Biology not been studied, individual genes or proteins at a particular time, such as the last 30 years has been successfully practiced. It examines the behavior and the relationship of all the elements in a particular biological system while it works.
  • To understand Biology on a systemic level, the structure and dynamics of the cellular functions and the functions of the organism, not the properties of isolated components of a cell or organism to be studied.
  • Systems biology attempts to predict the quantitative behavior of a biological process, which has been exposed to realistic problems, so that this quantitative method based his strength on the explicit inclusion of the components involved in the process, their interactions and realistic values ​​of their concentrations, whereabouts and conditions.
  • A discipline at the intersection of biology, mathematics and physics, which combines experimental and computational approaches emphasized in order to understand biological processes in cells, tissues and organisms.
  • Systems biology aims to arrive at a comprehensive quantitative understanding of the dynamic interactions between the constituents and components of a biological system in order to understand the behavior of the system as a whole and to allow predictions. To achieve this goal, mathematical concepts to biological systems are applied. Of central importance here is an iterative process between laboratory experiments and computer modeling.

History

  • The concept of integrative studies of biological systems is not new. A biological sub-area, in which analysis system operated for several decades, the ecology. The famous Lotka -Volterra equation of 1931 can already be seen as a systemic approach.
  • As a forerunner of systems biology, the General System Theory by Ludwig von Bertalanffy may be considered.
  • The meaning of systems biology was recognized by Norbert Wiener in 1948.
  • As pioneers of Systems Biology, the British neurophysiologist and Nobel laureate Alan Lloyd Hodgkin and Andrew Fielding Huxley, who laid in 1952 with the mathematical model of a nerve cell, the basis for the mathematical simulation of biological processes based on differential equations apply.
  • The breakthrough for systems biology came around the turn of the century through the development of high-throughput technologies for measuring gene expression, protein expression and protein-protein interaction at the molecular level and the completion of the Human Genome Project and many other genome projects. The flood of data obtained in this for about three billion base pairs and over one million proteins per cell makes it impossible to perform all theoretically conceivable and interesting experiments in the laboratory. Therefore, the computer modeling precondition for the selection of the most promising approaches has become.

The widespread use of the Internet was a basic requirement for a breakthrough in systems biology, as only the Internet to share the huge amount of data allowed in international cooperation.

The current state of science can be seen in specialized journals such as Molecular Systems Biology, as well as at numerous international conferences such as the ICSB pursue.

Methodological approaches

A systems biology approach comprises repeating cycles of experiments and hypothesis- driven modeling:

Based on these mathematical models, the behavior of a system can be predicted under certain conditions and, ultimately, new strategies are being developed to manipulate and control cells, which may eventually lead to development of new drugs.

Basically, there are

Currently being discussed in the philosophy of science to what extent one can transfer the philosophy of physics to that of systems biology. Obviously this is the research field of systems biology is an extension of classical molecular biology with mathematical methods. Since the mathematical modeling in systems biology plays a similarly important role as in physics, we initially thought we could transfer the epistemology of physics underlying the systems biology. However, there is a lack of systems biology to universal theories such as general relativity theory or Maxwell's fundamental equations of electrodynamics. It seems therefore to be necessary to develop their own philosophy of systems biology.

Mathematics and modeling

The base of the two approaches are differential equations which describe the variation of biological phenomena in a certain time t. Thus, for example, changes the membrane potential of a neuron according to the Hodgkin- Huxley model, among other things, as a function of ion currents of potassium and sodium:

Examples of systems biology

  • Principles of bacterial signaling networks:

Biochemical networks in cells need to function in a chaotic environment reliably with less than perfect components. Mark Kollman and colleagues were able to show in 2005 through a combination of experiments and computer modeling that Escherichia coli has the smallest sufficiently robust chemotactic system, which allows a precise chemotactic response of the organism, while the cost of the organism are minimized.

  • Distribution of hair follicles:

The uniform distribution of hair follicles has fascinated scientists for a long time. SICK and colleagues were able to show by means of a reaction - diffusion model, that the protein and its inhibitor WNK DKK can increase the density of hair follicles, and that other signal transduction pathways in the distribution pattern of the hair follicles are involved.

  • JAK -STAT signaling pathway:

JAK -STAT signaling pathway is involved in many pathways of lying on the cell surface receptors, such as epoxy. Swameye I. and colleagues were able to show by mathematical modeling of the JAK -STAT signaling pathway, that the STAT5 protein that experimental measurements can not be accessed periodically from the nucleus to the cytoplasm and is transported back.

Supported Projects

National

Systems biology and its method development is sustainably funded by the EU under the 6th and 7th Framework Programme. The Federal Ministry of Education and Research (BMBF ) since 2004 promotes the systems biology already in the framework of the research project HepatoSys ( Competence Network Systems Biology of Hepatocytes ).

Since January 2007, the BMBF supports the German Systems Biology with the program " Biotechnology - seize the opportunity and " FORSYS (Research Units for Systems Biology FORSYS ) with four centers for systems biology. The four FORSYS centers are located in Freiburg im Breisgau ( FRISYS - Freiburg Initiative for Systems Biology Speaker: Wolfgang R. Hess), Heidelberg ( VIROQUANT - Systems Biology of Virus -Cell Interactions ), Potsdam ( GoFORSYS ) and Magdeburg (in collaboration with the Max Planck Institute for Dynamics of Complex Technical Systems ). FORSYS is designed as a " lighthouse of the German Systems Biology " and "Corporate Partner of the Research Units of Systems Biology - FORSYS Partner" program expanded. Another large network of research projects funded by the Helmholtz Association since 2007. The " Helmholtz Alliance on Systems Biology " is mainly concerned with the study of causes of complex diseases. To him the Helmholtz centers DKFZ, FZJ, HZI, GSF, MDC and the UFZ are involved. In addition to scientists from the Helmholtz Association a variety of external partners are encouraged.

Transnational

SysMO ( " Systems Biology of Microorganisms" or " Systems Biology of Microorganisms " ) is a transnational initiative for research funding by the Federal Ministry for Education and Research together with the Federal Ministry for Education, Science and Culture in Austria, the Netherlands Organization for Scientific Research, the Science Council of Norway, the Ministry of Education and Science in Spain and the Science of Biotechnology and biological research in the UK is supported. The goal of SysMO is to establish a system biology of unicellular microorganisms. From Austria are 2, 29 from Germany, Norway 7, 9 from Spain, 15 from Netherlands, 22 from the UK, the Czech Republic 1, 2 from France and Switzerland four groups of the SysMO initiative.

Criticism

The Nobel Prize-winning biologist Sydney Brenner characterized the field in a paper called " low input, high throughput, no output science. "

Computersimulation Systems analysis Lotka–Volterra equation Andrew Huxley Denis Noble Defibrillation Cybernetics Hormone Dynamics (physics) Top-down and bottom-up design Hodgkin–Huxley model JAK-STAT signaling pathway Metabolic pathway Neuroinformatics Computational Neuroscience Petri net Closed-loop transfer function SBML Bioinformatics Science (journal) Stefan Schuster Nature Reviews Molecular Cell Biology Digital Object Identifier Integrated Authority File
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