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What is systems biology? From genes to function and back

  • Hans V. WesterhoffEmail author
  • Jan-Hendrik S. Hofmeyr
Chapter
Part of the Topics in Current Genetics book series (TCG, volume 13)

Abstract

The essence of the grand contributions of physiology and molecular biology to biology is discussed in relation to what may be needed to understand living systems. Unanswered is the link between function and molecular behaviour, and emergence of function from the nonlinear interactions, respectively. Systems biology should focus on properties that emerge in nonlinear interactions from the molecular level up, which are crucial for biological function. Pre-genomics approaches such as Metabolic and Hierarchical Control Analysis have already contributed concepts and conclusions to systems biology. Their combination with the genome-wide analyses should now lead to substantial progress in the understanding of life. An aspect of biology at odds with traditional physics and chemistry is the circular causation that occurs in all living systems. By analyzing this phenomenon quantitatively, systems biology can already deal with certain types of circular causation by dissection.

Keywords

Symmetry Breaking System Biology Control Coefficient Macroscopic State Metabolic Control Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1. Carlson JM, Doyle J (2002) Complexity and robustness. Proc Natl Acad Sci USA 99 Suppl 1:2538-2545 CrossRefGoogle Scholar
  2. 2. Cortassa S, Aon MA, Westerhoff HV (1991) Linear non-equilibrium thermodynamics describes the dynamics of an autocatalytic system. Biophys J 60:794-803 PubMedGoogle Scholar
  3. 3. Hill TL (1977) Free Energy Transduction in Biology. Academic Press New YorkGoogle Scholar
  4. 4. Hofmeyr J-HS, Westerhoff HV (2001) Building the cellular puzzle: Control in Multi-level reaction networks. J Theor Biol 20:261-285 CrossRefGoogle Scholar
  5. 5. Hornberg JJ, Bruggeman FJ, Binder B, Geest CR, Bij de Vaate AJM, Lankelma J, Heinrich R, Westerhoff HV (2005) Principles behind the multifarious control of signal transduction ERK phosphorylation and kinase/phosphatase control. FEBS J 1:244-258 CrossRefGoogle Scholar
  6. 6. Kacser H, Burns JA (1973) The Control of Flux. Symp Soc Exp Biol 27:65-104 PubMedGoogle Scholar
  7. 7. Kahn D, Westerhoff HV (1991) Control theory of regulatory cascades. J Theor Biol 153:255-285 PubMedGoogle Scholar
  8. 8. Katchalsky A, Curran P F (1967) Non-equilibrium thermodynamics in biophysics. Harvard University Press Cambridge MA, USAGoogle Scholar
  9. 9. Keizer J (1987) Statistical thermodynamics of non-equilibrium processes. Springer-Verlag BerlinGoogle Scholar
  10. 10. Maturana HR, Varela FJ (1980) Autopoiesis and cognition: The realisation of the living. D. Reidel Publishing Company DordrechtGoogle Scholar
  11. 11. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191:144-148 PubMedGoogle Scholar
  12. 12. Nicolis G and Prigogine I (1977) Self-organization in nonequilibrium systems. Wiley and Sons, New YorkGoogle Scholar
  13. 13. Reed JL Vo TD Schilling CH, Palsson BO (2003) An expanded genome-scale model of Escherichia coli K-12. Genome Biol 13:2423-2434 Google Scholar
  14. 14. Rosen R (1991) Life itself. Columbia University Press New YorkGoogle Scholar
  15. 15. Schuster S, Fell DA, Dandekar T (2000) A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol 18:326-232 CrossRefPubMedGoogle Scholar
  16. 16. Savageau MA (1976) Biochemical systems analysis. Addison-Wesley Reading MAGoogle Scholar
  17. 17. Teusink B, Walsh MC, Van Dam K, Westerhoff HV (1998) The danger of metabolic pathways with turbo design. Trends Biochem Sci 23:162-169 CrossRefPubMedGoogle Scholar
  18. 18. Westerhoff HV, Palsson BOP (2004) The evolution of molecular biology into systems biology. Nature Biotechnol 42:1249-1252CrossRefGoogle Scholar
  19. 19. Westerhoff HV, Van Dam K (1987) Thermodynamics and control of biological free-energy transduction. Elsevier AmsterdamGoogle Scholar
  20. 20. Wu L, Wang W, van Winden WA, van Gulik WM, Heijnen JJ (2004) A new framework for the estimation of control parameters in metabolic pathways using lin-log kinetics. Eur J Biochem 271:3348-3359CrossRefPubMedGoogle Scholar

Authors and Affiliations

  1. 1.Institute for Molecular Cell Biology and Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, De Boelelaan 1087, NL-1081 HV Amsterdam, EU 
  2. 2.Dept. of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, StellenboschSouth Africa

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