Skip to main content

Scientific Challenges in Systems Biology

  • Chapter
Introduction to Systems Biology

Abstract

Systems biology is the study of biological systems at the system level. Such studies are made possible by progress in molecular biology, genomics, computer science, and other fields that deal with the complexity of systems. For systems biology to grow into a mature scientific discipline, there must be basic principles or conceptual frameworks that drive scientific inquiry. The author argues that understanding the robustness of biological systems and the principles behind such phenomena is critically important for establishing the theoretical foundation of systems biology. It may be a guiding principle not only for basic scientific research but also for clinical studies and drug discovery. A series of technologies and methods need to be developed to support investigation of such theorydriven and experimentally verifiable research.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

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.

References

  1. Kitano H. Systems biology: a brief overview. Science 2002;295(5560):1662–1664.

    Article  PubMed  CAS  Google Scholar 

  2. Kitano H. Computational systems biology. Nature 2002;420(6912):206–210.

    Article  PubMed  CAS  Google Scholar 

  3. Cannon WB. The Wisdom of the Body, 2nd edition. New York: W.W. Norton; 1939.

    Google Scholar 

  4. Wiener N. Cybernetics: Or Control and Communication in the Animal and the Machine. Cambridge: The MIT Press; 1948.

    Google Scholar 

  5. Bertalanffy LV. General System Theory. New York: George Braziller; 1968.

    Google Scholar 

  6. Hasty J, McMillen D, Collins JJ. Engineered gene circuits. Nature 2002;420(6912):224–230.

    Article  PubMed  CAS  Google Scholar 

  7. Guelzim N, Bottani S, Bourgine P, et al. Topological and causal structure of the yeast transcriptional regulatory network. Nat Genet 2002;31(1):60–63.

    Article  PubMed  CAS  Google Scholar 

  8. Ideker T, Ozier O, Schwikowski B, et al. Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 2002;18Suppl 1:S233–S240.

    PubMed  Google Scholar 

  9. Ideker T, Thorsson V, Ranish JA, et al. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 2001;292(5518):929–934.

    Article  PubMed  CAS  Google Scholar 

  10. Ihmels J, Friedlander G, Bergmann S, et al. Revealing modular organization in the yeast transcriptional network. Nat Genet 2002;31(4):370–377.

    PubMed  CAS  Google Scholar 

  11. Ferrell JE, Jr. Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 2002;14(2):140–148.

    Article  PubMed  CAS  Google Scholar 

  12. Bhalla US, Iyengar R. Emergent properties of networks of biological signaling pathways. Science 1999;283(5400):381–387.

    Article  PubMed  CAS  Google Scholar 

  13. Tyson JJ, Chen K, Novak B. Network dynamics and cell physiology. Nat Rev Mol Cell Biol 2001;2(12):908–916.

    Article  PubMed  CAS  Google Scholar 

  14. Chen KC, Calzone L, Csikasz-Nagy A, et al. Integrative analysis of cell cycle control in budding yeast. Mol Biol Cell 2004;15(8):3841–3462.

    Article  PubMed  CAS  Google Scholar 

  15. Kitano H. Biological robustness. Nat Rev Genet 2004;5(11):826–837.

    Article  PubMed  CAS  Google Scholar 

  16. Little JW, Shepley DP, Wert DW. Robustness of a gene regulatory circuit. EMBO J 1999;18(15):4299–4307.

    Article  PubMed  CAS  Google Scholar 

  17. Alon U, Surette MG, Barkai N, et al. Robustness in bacterial chemotaxis. Nature 1999;397(6715):168–171.

    Article  PubMed  CAS  Google Scholar 

  18. Barkai N, Leibler S. Robustness in simple biochemical networks. Nature 1997;387(6636):913–917.

    Article  PubMed  CAS  Google Scholar 

  19. Yi TM, Huang Y, Simon MI, et al. Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci USA 2000;97(9):4649–4653.

    Article  PubMed  CAS  Google Scholar 

  20. von Dassow G, Meir E, Munro EM, Odell GM. The segment polarity network is a robust developmental module. Nature 2000;406(6792):188–192.

    Article  Google Scholar 

  21. Kitano H. Cancer as a robust system: implications for anticancer therapy. Nat Rev Cancer 2004;4(3):227–235.

    Article  PubMed  CAS  Google Scholar 

  22. Kitano H. Cancer robustness: tumour tactics. Nature 2003;426(6963):125.

    Article  PubMed  CAS  Google Scholar 

  23. Wagner GP, Altenberg L. Complex adaptations and the evolution of evolvability. Evolution 1996;50(3):967–976.

    Article  Google Scholar 

  24. Rutherford SL. Between genotype and phenotype: protein chaperones and evolvability. Nat Rev Genet 2003;4(4):263–274.

    Article  PubMed  CAS  Google Scholar 

  25. de Visser J, Hermission J, Wagner GP, et al. Evolution and Detection of Genetics Robustness. Evolution 2003;57(9):1959–1972.

    Article  PubMed  Google Scholar 

  26. Agrawal AA. Phenotypic plasticity in the interactions and evolution of species. Science 2001;294(5541):321–326.

    Article  PubMed  CAS  Google Scholar 

  27. Schlichting C, Pigliucci M. Phenotypic Evolution: A Reaction Norm Perspective. Sunderland: Sinauer Associates, Inc.; 1998.

    Google Scholar 

  28. Eldar A, Dorfman R, Weiss D, et al. Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 2002;419(6904):304–308.

    Article  PubMed  CAS  Google Scholar 

  29. Meir E, von Dassow G, Munro E, et al. Robustness, flexibility, and the role of lateral inhibition in the neurogenic network. Curr Biol 2002;12(10):778–786.

    Article  PubMed  CAS  Google Scholar 

  30. Schlosser G, Wagner G. Modularity in Development and Evolution. Chicago: The University of Chicago Press; 2004.

    Google Scholar 

  31. Rutherford SL, Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature 1998;396(6709):336–342.

    Article  PubMed  CAS  Google Scholar 

  32. Queitsch C, Sangster TA, Lindquist S. Hsp90 as a capacitor of phenotypic variation. Nature 2002;417(6889):618–624.

    Article  PubMed  CAS  Google Scholar 

  33. Siegal ML, Bergman A. Waddington’s canalization revisited: developmental stability and evolution. Proc Natl Acad Sci USA 2002;99(16):10528–10532.

    Article  PubMed  CAS  Google Scholar 

  34. Waddington CH. The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology. New York: Macmillan; 1957.

    Google Scholar 

  35. Csete ME, Doyle J. Bow ties, metabolism and disease. Trends Biotechnol 2004;22(9):446–450.

    Article  PubMed  CAS  Google Scholar 

  36. Ma HW, Zeng AP. The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 2003;19(11):1423–1430.

    Article  PubMed  CAS  Google Scholar 

  37. Oda K, Kitano H. A comprehensive pathway map of toll-like receptor signaling network. Mol Syst Biol 2:2006.0015. Epub 2006 Apr 18.

    Google Scholar 

  38. Oda K, Matsuoka Y, Funahashi, et al. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005;1:E1–17.

    Article  CAS  Google Scholar 

  39. Kitano H, Oda K. Self-extending symbiosis: a mechanism for increasing robustness through evolution. Biol Theory 2006;1(1):61–66.

    Article  Google Scholar 

  40. Kirschner M, Gerhart J. Evolvability. Proc Natl Acad Sci USA 1998;95(15):8420–8427.

    Article  PubMed  CAS  Google Scholar 

  41. Carlson JM, Doyle J. Highly optimized tolerance: a mechanism for power laws in designed systems. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 1999;60(2 Pt A):1412–4127.

    PubMed  CAS  Google Scholar 

  42. Carlson JM, Doyle J. Complexity and robustness. Proc Natl Acad Sci USA 2002;99Suppl 1:2538–2545.

    Article  PubMed  Google Scholar 

  43. Bak P, Tang C, Wiesenfeld K. Self-organized criticality. Phys Rev A 1988;38(1):364–374.

    Article  PubMed  Google Scholar 

  44. Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet 2004;5(2):101–113.

    Article  PubMed  CAS  Google Scholar 

  45. Kitano H, Kimura T, Oda K, et al. Metabolic syndrome and robustness tradeoffs. diabetes. 2004;53(Supplment 3):S1–S10.

    Google Scholar 

  46. Harris AL. Hypoxia-a key regulatory factor in tumour growth. Nat Rev Cancer 2002;2(1):38–47.

    Article  PubMed  CAS  Google Scholar 

  47. Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 2004;5(6):437–448.

    Article  PubMed  CAS  Google Scholar 

  48. Kitano H, Oda K. Robustness trade-offs and host-microbial symbiosis in the immune system. Mol Syst Biol 2006;doi:10. 038/msb4100039.

    Google Scholar 

  49. Kitano H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 2007;6(3):202–210.

    Article  PubMed  CAS  Google Scholar 

  50. Hucka M, Finney A, Sauro HM, et al. The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 2003;19(4):524–531.

    Article  PubMed  CAS  Google Scholar 

  51. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle J, Kitano H. The ERATO Systems Biology Workbench: enabling interaction and exchange between software tools for computational biology. Pac Symp Biocomput 2002:450–461.

    Google Scholar 

  52. Kitano H. Computational Cellular Dynamics: A Network-Physics Integral. Nat Rev Mol Cell Biol 2006;7:163.

    Article  CAS  Google Scholar 

  53. Balagadde FK, You L, Hansen CL, Arnold FH, Quake SR. Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 2005;309(5731):137–140.

    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 Humana Press Inc.

About this chapter

Cite this chapter

Kitano, H. (2007). Scientific Challenges in Systems Biology. In: Choi, S. (eds) Introduction to Systems Biology. Humana Press. https://doi.org/10.1007/978-1-59745-531-2_1

Download citation

Publish with us

Policies and ethics