Skip to main content

Introduction to systems biology

  • Chapter
Plant Systems Biology

Part of the book series: Experientia Supplementum ((EXS,volume 97))

  • 1525 Accesses

Abstract

The developments in the molecular biosciences have made possible a shift to combined molecular and system-level approaches to biological research under the name of Systems Biology. It integrates many types of molecular knowledge, which can best be achieved by the synergistic use of models and experimental data. Many different types of modeling approaches are useful depending on the amount and quality of the molecular data available and the purpose of the model. Analysis of such models and the structure of molecular networks have led to the discovery of principles of cell functioning overarching single species. Two main approaches of systems biology can be distinguished. Top-down systems biology is a method to characterize cells using system-wide data originating from the Omics in combination with modeling. Those models are often phenomenological but serve to discover new insights into the molecular network under study. Bottom-up systems biology does not start with data but with a detailed model of a molecular network on the basis of its molecular properties. In this approach, molecular networks can be quantitatively studied leading to predictive models that can be applied in drug design and optimization of product formation in bioengineering. In this chapter we introduce analysis of molecular network by use of models, the two approaches to systems biology, and we shall discuss a number of examples of recent successes in systems biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Reed JL, Vo TD, Schilling CH, Palsson BO (2003) An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol 4: R54

    Article  PubMed  Google Scholar 

  2. Keseler IM, Collado-Vides J, Gama-Castro S, Ingraham J, Paley S, Paulsen IT, Peralta-Gil M, Karp PD (2005) EcoCyc: a comprehensive database resource for Escherichia coli. Nucleic Acids Res 33: D334–337

    Article  PubMed  CAS  Google Scholar 

  3. Salgado H, Gama-Castro S, Peralta-Gil M, Diaz-Peredo E, Sanchez-Solano F, Santos-Zavaleta A, Martinez-Flores I, Jimenez-Jacinto V, Bonavides-Martinez C, Segura-Salazar J et al. (2006) RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions. Nucleic Acids Res 34: D394–397

    Article  PubMed  CAS  Google Scholar 

  4. Stelling J, Klamt S, Bettenbrock K, Schuster S, Gilles ED (2002) Metabolic network structure determines key aspects of functionality and regulation. Nature 420: 190–193

    Article  PubMed  CAS  Google Scholar 

  5. Forster J, Famili I, Fu P, Palsson BO, Nielsen J (2003) Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res 13: 244–253

    Article  PubMed  CAS  Google Scholar 

  6. Price ND, Reed JL, Palsson BO (2004) Genome-scale models of microbial cells: evaluating the consequences of constraints. Nat Rev Microbiol 2: 886–897

    Article  PubMed  CAS  Google Scholar 

  7. Bakker BM, Michels PAM, Opperdoes FR, Westerhoff HV (1997) Glycolysis in bloodstream from Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes. J Biol Chem 272: 3207–3215

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. Rohwer JM, Meadow ND, Roseman S, Westerhoff HV, 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  CAS  Google Scholar 

  10. Teusink B, Passarge J, Reijenga CA, Esgalhado E, van der Weijden CC, Schepper M, Walsh MC, Bakker BM, van Dam K, Westerhoff HV et al. (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  CAS  Google Scholar 

  11. Hoefnagel MH, Starrenburg MJ, Martens DE, Hugenholtz J, Kleerebezem M, Van S, II, Bongers R, Westerhoff HV, Snoep JL (2002) Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis. Microbiol 148: 1003–1013

    CAS  Google Scholar 

  12. Bruggeman FJ, Boogerd FC, Westerhoff HV (2005) The multifarious short-term regulation of ammonium assimilation of Escherichia coli: dissection using an in silico replica. Febs J 272: 1965–1985

    Article  PubMed  CAS  Google Scholar 

  13. Bakker BM, Mensonides FI, Teusink B, van Hoek P, Michels PA, Westerhoff HV (2000) Compartmentation protects trypanosomes from the dangerous design of glycolysis. Proc Natl Acad Sci USA 97: 2087–2092

    Article  PubMed  CAS  Google Scholar 

  14. Bruggeman FJ, Hornberg JJ, Bakker BM, Westerhoff HV (2005) Introduction to computational models of biochemical reaction networks. In: A Kriete, R Eils (eds): Computational Systems Biology, Elsevier

    Google Scholar 

  15. Cascante M, Boros LG, Comin-Anduix B, de Atauri P, Centelles JJ, Lee PW (2002) Metabolic control analysis in drug discovery and disease. Nat Biotechnol 20: 243–249

    Article  PubMed  CAS  Google Scholar 

  16. Michels PAM, Bakker BM, Opperdoes FR, Westerhoff HV (In press) On the mathematical modelling of metabolic pathways and its use in the identification of the most suitable drug target. In: H Vial, A Fairlamb, R Ridley (eds): Tropical disease guidelines and issues: discoveries and drug development, WHO, Geneva.

    Google Scholar 

  17. Tyson JJ, Chen K, Novak B (2001) Network dynamics and cell physiology. Nat Rev Mol Cell Biol 2: 908–916

    Article  PubMed  CAS  Google Scholar 

  18. Tyson JJ, Chen KC, Novak B (2003) Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol 15: 221–231

    Article  PubMed  CAS  Google Scholar 

  19. Selkov EE, Reich JG (1981) Energy metabolism of the cell. Academic Press, London

    Google Scholar 

  20. Westerhoff HV, Palsson BO (2004) The evolution of molecular biology into systems biology. Nat Biotechnol 22: 1249–1252

    Article  PubMed  CAS  Google Scholar 

  21. Alberghina L, Westerhoff HV (eds) (2005) Systems biology: definitions and perspectives (topics in current genetics), Springer-Verlag Berlin, Heidelberg GmbH

    Google Scholar 

  22. Bruggeman FJ, Westerhoff HV, Boogerd FC (2002) BioComplexity: a pluralist research strategy is necessary for a mechanistic explanation of the “live” state. Philosophical Psychology 15: 411–440

    Article  Google Scholar 

  23. Kauffman SA (1971) Articulation of parts explanations in biology. In: RC Buck, RS Cohen (eds): Boston studies in the philosophy of science. Kluver Academic Publishers, 257–272

    Google Scholar 

  24. Machamer P, Darden L, Craver CF (2000) Thinking about mechanisms. Philosophy of Science 67: 1–25

    Article  Google Scholar 

  25. Boogerd FC, Bruggeman FJ, Richardson R, Stephan S (2005) Emergence and its place in nature: A case study of biochemical networks. Synthese 145: 131–164

    Article  Google Scholar 

  26. Darden L, Maull N (1977) Interfield theories. Philosophy of Sci 44: 43–64

    Article  Google Scholar 

  27. Auyang SY (1998) Foundation of complex-system theories: in economics, evolutionary biology, and statistical physics. Cambridge University Press, Cambridge

    Google Scholar 

  28. Tyson JJ, Novak B, Odell GM, Chen K, Thron CD (1996) Chemical kinetic theory: Understanding cell cycle regulation. Trends Biochem Sci 21: 89–96

    Article  PubMed  CAS  Google Scholar 

  29. Olivier BG, Snoep JL (2004) Web-based kinetic modelling using JWS Online. Bioinformatics 20: 2143–2144

    Article  PubMed  CAS  Google Scholar 

  30. Snoep JL, Bruggeman F, Olivier BG, Westerhoff HV (2005) Towards building the silicon cell: A modular approach. Biosystems 83: 207–216

    Article  PubMed  CAS  Google Scholar 

  31. Cornish-Bowden A (1995) Fundamentals of enzyme kinetics. Portland Press, London

    Google Scholar 

  32. Westerhoff HV, Van Dam K (1987) Thermodynamics and control of biological free-energy transduction. Elsevier Science Publishers BV (Biomedical Division), Amsterdam

    Google Scholar 

  33. Alberty RA (2002) Thermodynamics of systems of biochemical reactions. J Theor Biol 215: 491–501

    Article  PubMed  CAS  Google Scholar 

  34. Kacser H, Burns JA (1973) The control of flux. Symp Soc Exp Biol 27: 65–104

    PubMed  CAS  Google Scholar 

  35. Heinrich R, Rapoport TA (1974) A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. Eur J Biochem 42: 89–95

    Article  PubMed  CAS  Google Scholar 

  36. Fell DA (1997) Understanding the control of metabolism, First Edition. Portland Press, London and Miami

    Google Scholar 

  37. Westerhoff HV, Chen YD (1984) How do enzyme activities control metabolite concentrations? An additional theorem in the theory of metabolic control. Eur J Biochem 142: 425–430

    Article  PubMed  CAS  Google Scholar 

  38. Kahn D, Westerhoff HV (1991) Control theory of regulatory cascades. J Theor Biol 153: 255–285

    Article  PubMed  CAS  Google Scholar 

  39. Hofmeyr JH, Westerhoff HV (2001) Building the cellular puzzle: control in multi-level reaction networks. J Theor Biol 208: 261–285

    Article  PubMed  CAS  Google Scholar 

  40. Van Kampen NG (1992) Stochastic processes in chemistry and physics. North-Holland, Amsterdam

    Google Scholar 

  41. Elf J, Ehrenberg M (2003) Fast evaluation of fluctuations in biochemical networks with the linear noise approximation. Genome Res 13: 2475–2484

    Article  PubMed  CAS  Google Scholar 

  42. Reder C (1988) Metabolic control theory: a structural approach. J Theor Biol 135: 175–201

    Article  PubMed  CAS  Google Scholar 

  43. Kholodenko BN, Westerhoff HV, Puigjaner J, Cascante M (1995) Control in channeled pathways — a matrix-method calculating the enzyme control coefficients. Biophys Chem 53: 247–258

    Article  PubMed  CAS  Google Scholar 

  44. Westerhoff HV, Kell DB (1996) What bio technologists knew all along? J Theor Biol 182: 411–420

    Article  PubMed  CAS  Google Scholar 

  45. Hornberg JJ, Bruggeman FJ, Binder B, Geest CR, de Vaate AJ, Lankelma J, Heinrich R, Westerhoff HV (2005b) Principles behind the multifarious control of signal transduction. ERK phosphorylation and kinase/phosphatase control. Febs J 272: 244–258

    Article  PubMed  CAS  Google Scholar 

  46. Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95: 14863–14868

    Article  PubMed  CAS  Google Scholar 

  47. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9: 3273–3297

    PubMed  CAS  Google Scholar 

  48. Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L (2001) Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292: 929–934

    Article  PubMed  CAS  Google Scholar 

  49. Daran-Lapujade P, Jansen ML, Daran JM, van Gulik W, de Winde JH, Pronk JT (2004) Role of transcriptional regulation in controlling fluxes in central carbon metabolism of Saccharomyces cerevisiae. A chemostat culture study. J Biol Chem 279: 9125–9138

    Article  PubMed  CAS  Google Scholar 

  50. Ihmels JH, Bergmann S (2004) Challenges and prospects in the analysis of large-scale gene expression data. Brief Bioinform 5: 313–327

    Article  PubMed  CAS  Google Scholar 

  51. Chassagnole C, Noisommit-Rizzi N, Schmid JW, Mauch K, Reuss M (2002) Dynamic modeling of the central carbon metabolism of Escherichia coli. Biotechnol Bioeng 79: 53–73

    Article  CAS  PubMed  Google Scholar 

  52. Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW (2003) The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol 1: E10

    Article  PubMed  Google Scholar 

  53. Ideker T, Galitski T, Hood L (2001) A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2: 343–372

    Article  PubMed  CAS  Google Scholar 

  54. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5: 101–113

    Article  PubMed  CAS  Google Scholar 

  55. Albert R, Barabasi AL (2002) Statistical mechanics of complex networks. Revs Mod Physics 74: 47–97

    Article  Google Scholar 

  56. Newman MEJ (2003) The structure and function of complex networks. SIAM Rev 45: 167–256

    Article  Google Scholar 

  57. Fell DA, Wagner A (2000) The small world of metabolism. Nat Biotechnol 18: 1121–1122

    Article  PubMed  CAS  Google Scholar 

  58. Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407: 651–654

    Article  PubMed  CAS  Google Scholar 

  59. Ravasz E, Somera AL, Mongru DA, Oltvai ZN, Barabasi AL (2002) Hierarchical organization of modularity in metabolic networks. Science 297: 1551–1555

    Article  PubMed  CAS  Google Scholar 

  60. Tanay A, Sharan R, Kupiec M, Shamir R (2004) Revealing modularity and organization in the yeast molecular network by integrated analysis of highly heterogeneous genomewide data. Proc Natl Acad Sci USA 101: 2981–2986

    Article  PubMed  CAS  Google Scholar 

  61. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298: 824–827

    Article  PubMed  CAS  Google Scholar 

  62. Shen-Orr SS, Milo R, Mangan S, Alon U (2002) Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 31: 64–68

    Article  PubMed  CAS  Google Scholar 

  63. Yeger-Lotem E, Sattath S, Kashtan N, Itzkovitz S, Milo R, Pinter RY, Alon U, Margalit H (2004) Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. Proc Natl Acad Sci USA 101: 5934–5939

    Article  PubMed  CAS  Google Scholar 

  64. Schuster S, Dandekar T, Fell DA (1999) Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering. Trends Biotechnol 17: 53–60

    Article  PubMed  CAS  Google Scholar 

  65. 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  CAS  Google Scholar 

  66. Covert MW, Schilling CH, Palsson B (2001) Regulation of gene expression in flux balance models of metabolism. J Theor Biol 213: 73–88

    Article  PubMed  CAS  Google Scholar 

  67. Papin JA, Stelling J, Price ND, Klamt S, Schuster S, Palsson BO (2004) Comparison of network-based pathway analysis methods. Trends Biotechnol 22: 400–405

    Article  PubMed  CAS  Google Scholar 

  68. Garfinkel D, Hess B (1964) Metabolic control mechanisms. Vii.A Detailed computer model of the glycolytic pathway in ascites cells. J Biol Chem 239: 971–983

    PubMed  CAS  Google Scholar 

  69. Rapoport TA, Heinrich R, Jacobasc G, Rapoport S (1974) Linear steady-state treatment of enzymatic chains — mathematical-model of glycolysis of human erythrocytes. Eur J Biochem 42: 107–120

    Article  PubMed  CAS  Google Scholar 

  70. Guckenheimer J, Holms P (1983) Nonlinear oscillations, dynamical systems, and bifurcations of vector fields. Springer-Verlag, New York

    Google Scholar 

  71. Nicolis G, Prigogine I (1977) Self-organization in nonequilibrium systems: from dissipative structures to order through fluctuations. John Wiley & Sons, New York

    Google Scholar 

  72. Nicolis G, Prigogine I (1989) Exploring complexity: An introduction. WH Freeman & Co. San Francisco

    Google Scholar 

  73. Lefever R, Nicolis G (1971) Chemical instabilities and sustained oscillations. J Theor Biol 30: 267–284

    Article  PubMed  CAS  Google Scholar 

  74. Goldbeter A, Lefever R (1972) Dissipative structures for an allosteric model — application to glycolytic oscillations. Biophysical J 12: 1302

    CAS  Google Scholar 

  75. Selkov E (1975) Stabilization of energy charge, generation of oscillations and multiple steady states in energy metabolism as a result of purely stoichiometric regulation. Eur J Biochem 59: 151–157

    Article  CAS  Google Scholar 

  76. Goldbeter A (1997) Biochemical oscillations and cellular rhythms: the molecular bases of periodic and chaotic behaviour. Cambridge University Press, Cambridge

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  78. Reijenga KA, van Megen YM, Kooi BW, Bakker BM, Snoep JL, van Verseveld HW, Westerhoff HV (2005) Yeast glycolytic oscillations that are not controlled by a single oscillophore: a new definition of oscillophore strength. J Theor Biol 232: 385–398

    PubMed  CAS  Google Scholar 

  79. Kremling A, Bettenbrock K, Laube B, Jahreis K, Lengeler JW, Gilles ED (2001) The organization of metabolic reaction networks. III. Application for diauxic growth on glucose and lactose. Metab Eng 3: 362–379

    Article  PubMed  CAS  Google Scholar 

  80. Teusink B, Walsh MC, van Dam K, Westerhoff HV (1998) The danger of metabolic pathways with turbo design. Trends Biochem Sci 23: 162–169

    Article  PubMed  CAS  Google Scholar 

  81. Teusink B, Passarge J, Reijenga CA, Esgalhado E, Van der Weijden CC, Schepper M, Walsh MC, Bakker BM, Van Dam K, Westerhoff HV et al. (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  CAS  Google Scholar 

  82. ter Kuile BH, Westerhoff HV (2001) Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway. FEBS Lett 500: 169–171

    Article  PubMed  Google Scholar 

  83. Even S, Lindley ND, Cocaign-Bousquet M (2003) Transcriptional, translational and metabolic regulation of glycolysis in Lactococcus lactis subsp. cremoris MG 1363 grown in continuous acidic cultures. Microbiol 149: 1935–1944

    Article  CAS  Google Scholar 

  84. Rossell S, van der Weijden CC, Kruckeberg AL, Bakker BM, Westerhoff HV (2005) Hierarchical and metabolic regulation of glucose influx in starved Saccharomyces cerevisiae. FEMS Yeast Res 5: 611–619

    Article  PubMed  CAS  Google Scholar 

  85. Rhee SG, Chock PB, Stadtman ER (1989) Regulation of Escherichia coli glutamine synthetase. Adv Enzymol Relat Areas Mol Biol 62: 37–92

    Article  PubMed  CAS  Google Scholar 

  86. Ninfa AJ, Jiang P, Atkinson MR, Peliska JA (2000) Integration of antagonistic signals in the regulation of nitrogen assimilation in Escherichia coli. Curr Top Cell Regul 36: 31–75

    PubMed  CAS  Google Scholar 

  87. Kustu S, Hirschman J, Burton D, Jelesko J, Meeks JC (1984) Covalent modification of bacterial glutamine synthetase: physiological significance. Mol Gen Genet 197: 309–317

    Article  PubMed  CAS  Google Scholar 

  88. Hoffmann A, Levchenko A, Scott ML, Baltimore D (2002) The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298: 1241–1245

    Article  PubMed  CAS  Google Scholar 

  89. Schoeberl B, Eichler-Jonsson C, Gilles ED, Muller G (2002) Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nat Biotechnol 20: 370–375

    Article  PubMed  Google Scholar 

  90. Hornberg JJ, Binder B, Bruggeman FJ, Schoeberl B, Heinrich R, Westerhoff HV (2005) Control of MAPK signalling: from complexity to what really matters. Oncogene 24: 5533–5542

    Article  PubMed  CAS  Google Scholar 

  91. Kruger R, Heinrich R (2004) Model reduction and analysis of robustness for the Wnt/beta-catenin signal transduction pathway. Genome Inform Ser Workshop Genome Inform 15: 138–148

    Google Scholar 

  92. Borisov NM, Markevich NI, Hoek JB, Kholodenko BN (2005) Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexity. Biophys J 89: 951–966

    Article  PubMed  CAS  Google Scholar 

  93. Conzelmann H, Saez-Rodriguez J, Sauter T, Kholodenko BN, Gilles ED (2006) A domain-oriented approach to the reduction of combinatorial complexity in signal transduction networks. BMC Bioinformatics 7: 34

    Article  PubMed  CAS  Google Scholar 

  94. Ferrell JE Jr, Machleder EM (1998) The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280: 895–898

    Article  PubMed  CAS  Google Scholar 

  95. Bagowski CP, Ferrell JE Jr (2001) Bistability in the JNK cascade. Curr Biol 11: 1176–1182

    Article  PubMed  CAS  Google Scholar 

  96. Brandman O, Ferrell JE Jr, Li R, Meyer T (2005) Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science 310: 496–498

    Article  PubMed  CAS  Google Scholar 

  97. Pomerening JR, Kim SY, Ferrell JE Jr (2005) Systems-level dissection of the cell-cycle oscillator: bypassing positive feedback produces damped oscillations. Cell 122: 565–578

    Article  PubMed  CAS  Google Scholar 

  98. Rosenfeld N, Elowitz MB, Alon U (2002) Negative autoregulation speeds the response times of transcription networks. J Mol Biol 323: 785–793

    Article  PubMed  CAS  Google Scholar 

  99. Mangan S, Alon U (2003) Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA 100: 11980–11985

    Article  PubMed  CAS  Google Scholar 

  100. Mangan S, Zaslaver A, Alon U (2003) The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J Mol Biol 334: 197–204

    Article  PubMed  CAS  Google Scholar 

  101. Dekel E, Mangan S, Alon U (2005) Environmental selection of the feed-forward loop circuit in gene-regulation networks. Phys Biol 2: 81–88

    Article  PubMed  CAS  Google Scholar 

  102. Mangan S, Itzkovitz S, Zaslaver A, Alon U (2006) The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli. J Mol Biol 356: 1073–1081

    Article  PubMed  CAS  Google Scholar 

  103. Pomerening JR, Sontag ED, Ferrell JE Jr (2003) Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nat Cell Biol 5: 346–351

    Article  PubMed  CAS  Google Scholar 

  104. Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell. Science 297: 1183–1186

    Article  PubMed  CAS  Google Scholar 

  105. Ozbudak EM, Thattai M, Kurtser I, Grossman AD, van Oudenaarden A (2002) Regulation of noise in the expression of a single gene. Nat Genet 31: 69–73

    Article  PubMed  CAS  Google Scholar 

  106. Swain PS, Elowitz MB, Siggia ED (2002) Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc Natl Acad Sci USA 99: 12795–12800

    Article  PubMed  CAS  Google Scholar 

  107. Paulsson J (2004) Summing up the noise in gene networks. Nature 427: 415–418

    Article  PubMed  CAS  Google Scholar 

  108. Thattai M, van Oudenaarden A (2004) Stochastic gene expression in fluctuating environments. Genetics 167: 523–530

    Article  PubMed  Google Scholar 

  109. Golding I, Paulsson J, Zawilski SM, Cox EC (2005) Real-time kinetics of gene activity in individual bacteria. Cell 123: 1025–1036

    Article  PubMed  CAS  Google Scholar 

  110. Pedraza JM, van Oudenaarden A (2005) Noise propagation in gene networks. Science 307: 1965–1969

    Article  PubMed  CAS  Google Scholar 

  111. Rosenfeld N, Young JW, Alon U, Swain PS, Elowitz MB (2005) Gene regulation at the single-cell level. Science 307: 1962–1965

    Article  PubMed  CAS  Google Scholar 

  112. Elf J, Paulsson J, Berg OG, Ehrenberg M (2003) Near-critical phenomena in intracellular metabolite pools. Biophys J 84: 154–170

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Bruggeman, F.J., Hornberg, J.J., Boogerd, F.C., Westerhoff, H.V. (2007). Introduction to systems biology. In: Baginsky, S., Fernie, A.R. (eds) Plant Systems Biology. Experientia Supplementum, vol 97. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7439-6_1

Download citation

Publish with us

Policies and ethics