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From isolation to integration, a systems biology approach for building the Silicon Cell

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Part of the book series: Topics in Current Genetics ((TCG,volume 13))

Abstract

In the last decade, the field now commonly referred to as systems biology has developed rapidly. With the sequencing of whole genomes and the development of analysis methods to measure many of the cellular components, we have now entered the realm of complete descriptions at a cellular level. Although we have been seeing that larger and larger systems were being described, making a description complete is much more important than just adding additional components. The possibility of making complete descriptions will cause a paradigm shift in our approaches, on a theoretical, as well as a modeling and an experimental level. We will here present our view on systems biology and specifically focus on modeling strategies to build cellular models on the basis of detailed enzyme kinetic information: an approach advocated in the Silicon Cell project (http://www.siliconcell.net) making use of the JWS Online database of kinetic models (http://jjj.biochem.sun.ac.za).

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References

  • 1. Bakker BM, Assmus, HE, Bruggeman F, Haanstra JR, Klipp E, Westerhoff HV (2002) Network-based selectivity of antiparasitic inhibitors. Mol Biol Rep 29:1-52

    Article  PubMed  Google Scholar 

  • 2. Bhartiya S, Rawool S, Venkatesh, KV (2003) Dynamic model of Escherichia coli tryptophan operon shows an optimal structural design. Eur J Biochem 270:2644-2651

    Article  PubMed  Google Scholar 

  • 3. Chassagnole C, Fell DA, Rais B, Kudla B, Mazat J-P (2001) Control of the threonine-synthesis pathway in Escherichia coli: a theoretical and experimental approach. Biochem J 356:415-423

    Article  PubMed  Google Scholar 

  • 4. Clarke BL (1981) Complete set of steady states for the general stoichiometric dynamical system. J Chem Phys 75:4970-4979

    Article  Google Scholar 

  • 5. Cronwright GR, Rohwer JM, Prior BA (2003) Metabolic control analysis of glycerol synthesis in Saccharomyces cerevisiae. Appl Environ Microbiol 68:4448-4456

    Article  Google Scholar 

  • 6. Curien G, Ravanel S, Dumas R (2003) A kinetic model of the branch-point between the methionine and threonine biosynthesis pathways in Arabidopsis thaliana. Eur J Biochem 270:1-13

    Article  Google Scholar 

  • 7. De la Fuente A, Snoep JL, Westerhoff HV, Mendes P (2002) Metabolic control in integrated biochemical systems. Eur J Biochem 269:4399-4408

    Article  PubMed  Google Scholar 

  • 8. Galazzo JL, Bailey JE (1990) Fermentation pathway kinetics and metabolic flux control in suspended and immobilized Saccharomyces cerevisiae. Enz Microb Technol. 12:162-172

    Google Scholar 

  • 9. Heinrich R, Rapoport TA (1974) A linear steady-state treatment of enzymatic chains. Eur J Biochem 42:89-95

    Article  PubMed  Google Scholar 

  • 10. Helfert S, Estevez AM, Bakker B, Michels P, Clayton C (2001) Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei. Biochem J 357: 117-125

    Article  PubMed  Google Scholar 

  • 11. Hofmeyr JHS, Westerhoff HV (2001) Building the cellular puzzle. J Theor Biol 208:261-285

    Article  PubMed  Google Scholar 

  • 12. Hoefnagel MHN, Starrenburg MJC, Martens DE, Hugenholtz J, Kleerebezem M, Van Swam II, Bongers R, Westerhoff HV, Snoep JL (2002) Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis. Microbiology 148: 1003-1013.

    PubMed  Google Scholar 

  • 13. Hoefnagel MHN, Van Der Burgt A, Martens DE, Hugenholtz J, Snoep JL (2002) Time dependent responses of glycolytic intermediates in a detailed glycolytic model of Lactococcus lactis during glucose run-out experiments. Mol Biol Rep 29: 157-161

    Article  PubMed  Google Scholar 

  • 14. Holzhütter H-G (2004) The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks. Eur J Biochem 271:2905-2922

    Article  PubMed  Google Scholar 

  • 15. Hynne F, Dano S, Sorensen PG (2001) Full-scale model of glycolysis in Saccharomyces cerevisiae. Biophys Chem 94:121-163

    Article  PubMed  Google Scholar 

  • 16. Kacser H, Burns JA (1973) The control of flux. In: Davies DD (ed) Rate control of biological processes. Cambridge University Press, London, pp 65-104

    Google Scholar 

  • 17. Kholodenko BN, Demin OV, Moehren G, Hoek JB (1999) Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor J Biol Chem 274:30169-30181

    Google Scholar 

  • 18. Koster JG, Destrée OHJ, Westerhoff HV (1988) Kinetics of Histone Gene Expression during Early Development of Xenopus laevis. J Theor Biol 135:139-167

    PubMed  Google Scholar 

  • 19. Lambeth MJ, Kushmerick MJ, (2002) A Computational Model for Glycogenolysis in Skeletal Muscle Ann Biomed Eng 30: 808-827

    Google Scholar 

  • 20. Maher AD, Kuchel PW, Ortega F, de Atauri P, Centelles J, Cascante M (2003) Mathematical modelling of the urea cycle. Eur J Biochem 270, 3953-3961

    Google Scholar 

  • 21. Martins AM, Mendes P, Cordeiro C, Freire AP (2001) In situ kinetic analysis of glyoxalase I and glyoxalase II in Saccharomyces cerevisiae. Eur J Biochem 268:3930-3936

    Article  PubMed  Google Scholar 

  • 22. Mendes P (1997) Biochemistry by numbers: simulation of biochemical pathways with Gepasi 3. TIBS 22:361-363

    PubMed  Google Scholar 

  • 23. Mulquiney PJ, Kuchel PW, (1999) Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: computer simulation and metabolic control analysis. Biochem J 342: 597-604

    Article  PubMed  Google Scholar 

  • 24. Poolman MG, Fell DA, Thomas S (2000) Modelling photosynthesis and its control. J Exp Bot 51:319-328

    Article  Google Scholar 

  • 25. Olivier BG and Snoep JL( 2004) Web-based kinetic modelling using JWS Online. Bioinformatics 20:2143-2144

    Article  PubMed  Google Scholar 

  • 26. Olivier BG, Rohwer JM, Hofmeyr JHS (2002) Modelling cellular processes with Python and Scipy. Mol Biol Rep 29:249-254

    Article  PubMed  Google Scholar 

  • 27. Olsen LF, Hauser MJB, Kummer U, (2003) Mechanism of protection of peroxidase activity by oscillatory dynamics. Eur J Biochem 270:2796-2804

    Article  PubMed  Google Scholar 

  • 28. Price ND, Papin JA, Schilling CH, Palsson BO (2003) Genome-scale microbial in silico models: the constraints-based approach. TRENDS Biotechnol 21:162-169

    Article  PubMed  Google Scholar 

  • 29. Richard P, Bakker BM, Teusink B, Westerhoff HV, Van Dam K (1993) Synchronisation of glycolytic oscillations in intact yeast cells. In: Schuster S, Rigoulet M, Ouhabi R, Mazat JP (Eds) Modern trends in Biothermokinetics. Plenum Press, London, pp: 413-416

    Google Scholar 

  • 30. Richard P, Teusink B, Westerhoff HV, Van Dam K (1994) Around the growth phase transition S. cerevisiae's make-up favours sustained oscillations of intracellular metabolites. FEBS Lett 318:80-82

    Article  Google Scholar 

  • 31. Richard P, Teusink B, Van Dam K, Westerhoff HV (1996) Acetaldehyde mediates the synchronization of sustained glycolytic oscillations in yeast-cell populations. Eur J Biochem 235:238-241

    Article  PubMed  Google Scholar 

  • 32. Reijenga K (2002) Dynamic control of yeast glycolysis. PhD thesis, Vrije Universiteit Amsterdam.

    Google Scholar 

  • 33. Rohwer JM, Meadow ND, Roseman S, Westerhoff HV and Postma PW (2000) Understanding glucose transport by the bacterial phosphoenolpyruvate:glycose phosphotransferase system on the basis of kinetic measurements in vitro. J Biol Chem 275:34909-34921

    Article  PubMed  Google Scholar 

  • 34. Rohwer JM, Botha FC (2001) Analysis of sucrose accumulation in the sugar cane culm on the basis of in vitro kinetic data. Biochem J 358:437-445

    Article  PubMed  Google Scholar 

  • 35. Sauro HM (1991) SCAMP: a general-purpose simulator and metabolic control analysis program. CABIOS 9:441-450

    Google Scholar 

  • 36. Sauro HM (2000) Jarnac: a system for interactive metabolic analysis. In: Hofmeyr JHSH, Rohwer JM, Snoep JL (eds) Animating the cellular map: Proceedings of the 9th international meeting on biothermokinetics. Stellenbosch University Press, Stellenbosch, pp: 221-228

    Google Scholar 

  • 37. Schilling CH, Letscher D, Palsson BO (2000) Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. J Theor Biol 203:229-248

    Article  PubMed  Google Scholar 

  • 38. Schuster S, Fell DA, Dandekar T (2000) A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nature Biotech 18:326-332

    Article  Google Scholar 

  • 39. Schuster S, Hilgetag C (1994) On elementary flux modes in biochemical reaction systems in steady state. J Biol Syst 2:165-182

    Article  Google Scholar 

  • 40. Snoep JL, Hoefnagel MHN, Westerhoff HV (2004) Metabolic engineering of branched systems: redirecting the main pathway flux. In: Westerhoff HV, Kholodenko B (eds) Metabolic engineering in the post-genomic era. Horizon Scientific Press, Norwich, UK pp 357-377

    Google Scholar 

  • 41. Teusink B, Passarge J, Reijenga CA, Esgalhado E, Van der Weijden CC, Schepper M, Walsh MC, Bakker BM, Van Dam K, Westerhoff HV, Snoep JL (2000) Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur J Biochem 267:5313-5329

    Article  PubMed  Google Scholar 

  • 42. Tyson JJ, Novak B (2001) Regulation of the eukaryotic cell cycle: Molecular antagonism, hysteresis, and irreversible transitions. J Theor Biol 210:249-263

    Article  PubMed  Google Scholar 

  • 43. Westerhoff HV, Van Dam (1987) Thermodynamics and control in biological free-energy transduction. Elsevier, Amsterdam, The Netherlands.

    Google Scholar 

  • 44. Wiechert W (2001) 13C metabolic flux analysis. Metab Eng 3:95-206

    Google Scholar 

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Correspondence to Jacky L. Snoep .

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Lila Alberghina H.V. Westerhoff

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Snoep, J.L., Westerhoff, H.V. From isolation to integration, a systems biology approach for building the Silicon Cell. In: Alberghina, L., Westerhoff, H. (eds) Systems Biology. Topics in Current Genetics, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b106456

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