Abstract

Systems biology, possibly the latest sub-discipline of biology, has arisen as a result of the shockwave of genomic and proteomic data that has appeared in the past few years. However, despite ubiquitous initiatives that carry this label, there is no precise definition of systems biology other than the implication of a new, all-encompassing, multidisciplinary endeavor. Here we propose that systems biology is more than the integration of biology with methods of the physical and computational sciences, and also more than the expansion of the single-pathway approach to embracing genome-scale networks. It is the discipline that specifically addresses the fundamental properties of the complexity that living systems represent. To facilitate the discussion, we dissect and project the multifaceted systems complexity of living organisms into five dimensions: (1) molecular complexity; (2) structural complexity; (3) temporal complexity; (4) abstraction and emergence; and (5) algorithmic complexity. This “five-dimensional space” may provide a framework for comparing, classifying, and complementing the vast diversity of existing systems biology programs and their goals, and will also give a glimpse of the magnitude of the scientific problems associated with unraveling the ultimate mysteries of life.

References

  1. Aebersold R (2005) Molecular systems biology: a new journal for a new biology? Mol Sys Biol 1:msb4100009 E1–E2Google Scholar
  2. Aebersold R, Hood LE, Watts JD (2000) Equipping scientists for the new biology. Nat Biotechnol 18:359PubMedGoogle Scholar
  3. Albert R, Jeong H, Barabasi AL (2000) Error and attack tolerance of complex networks. Nature 406:378–382PubMedGoogle Scholar
  4. Alon U (2003) Biological networks: the tinkerer as an engineer. Science 301:1866–1867PubMedGoogle Scholar
  5. Alon U, Surette MG, Barkai N, Leibler S (1999) Robustness in bacterial chemotaxis. Nature 397:168–171PubMedGoogle Scholar
  6. Anderson PW (1972) More is different: broken symmetry and the nature of the hierarchical structure of science. Science 177:393–396PubMedGoogle Scholar
  7. Ashby WR (1964) An introduction to cybernetics. Routledge, Kegan and Paul, LondonGoogle Scholar
  8. Autumn K, Ryan MJ, Wake DB (2002) Integrating historical and mechanistic biology enhances the study of adaptation. Q Rev Biol 77:383–408PubMedGoogle Scholar
  9. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004) Bacterial persistence as a phenotypic switch. Science 305:1622–1625PubMedGoogle Scholar
  10. Ball P (2001) The self-made tapestry: pattern formation in nature. Oxford University Press, OxfordGoogle Scholar
  11. Bar-Yam Y (1997) Dynamics of complex systems. Perseus Books, ReadingGoogle Scholar
  12. Bar-Yam Y (2004) Multiscale variety in complex systems. Complexity 9:37–45Google Scholar
  13. Barabasi AL, Albert R (1999) Emergence of scaling in random networks. Science 286:509–512PubMedGoogle Scholar
  14. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5:101–113PubMedGoogle Scholar
  15. Barkai N, Leibler S (2000) Circadian clocks limited by noise. Nature 403:267–268PubMedGoogle Scholar
  16. Blackett PMS (1963) Memories of Rutherford. In: Birks JB (ed) Rutherford at Manchester. Benjamin, New York, p 108Google Scholar
  17. Bassingthwaighte JB, Liebovitch LS, West BJ (1994) Fractal physiology. Oxford University Press, New YorkGoogle Scholar
  18. Braich RS, Chelyapov N, Johnson C, Rothemund PWK, Adleman L (2002) Solution of a 20-variable 3-SAT problem on a DNA computer. Science 296:499–502PubMedGoogle Scholar
  19. Bray D (1997) Reductionism for biochemists: how to survive the protein jungle. Trends Biochem Sci 22:325–326PubMedGoogle Scholar
  20. Brent R (2000) Genomic biology. Cell 100:169–183PubMedGoogle Scholar
  21. Brown JH, Gupta VK, Li BL, Milne BT, Restrepo C, West GB (2002) The fractal nature of nature: power laws, ecological complexity and biodiversity. Philos Trans R Soc Lond B Biol Sci 357:619–626PubMedGoogle Scholar
  22. Carlson JM, Doyle J (2002) Complexity and robustness. Proc Natl Acad Sci USA 99:2538–2545PubMedGoogle Scholar
  23. Cauwenberghs G (1995) A micropower CMOS algorithmic A/D/A converter. IEEE T Circuits Syst I 42:913–919Google Scholar
  24. Cherry EM, Greenside HS, Henriquez CS (2000) A space-time adaptive method for simulating complex cardiac dynamics. Phys Rev Lett 84:1343–1346PubMedGoogle Scholar
  25. Corning PA (2002) The re-emergence of “emergence”: a venerable concept in search of a theory. Complexity 7:18–30Google Scholar
  26. Cross SS (1997) Fractals in pathology. J Pathol 182:1–8PubMedGoogle Scholar
  27. Cummings DAT, Irizarry RA, Huang NE, Endy TP, Nisalak A, Ungchusak K, Burke DS (2004) Travelling waves in the occurrence of dengue haemorrhagic fever in Thailand. Nature 427:344–347PubMedGoogle Scholar
  28. D'haeseleer P, Liang SD, Somogyi R (2000) Genetic network inference: from co-expression clustering to reverse engineering. Bioinformatics 16:707–726PubMedGoogle Scholar
  29. Davidson EH, Rast JP, Oliveri P, Ransick A, Calestani C, Yuh CH, Minokawa T, Amore G, Hinman V, Arenas-Mena C, Otim O, Brown CT, Livi CB, Lee PY, Revilla R, Rust AG, Pan ZJ, Schilstra MJ, Clarke PJC, Arnone MI, Rowen L, Cameron RA, McClay DR, Hood L, Bolouri H (2002) A genomic regulatory network for development. Science 295:1669–1678PubMedGoogle Scholar
  30. Dawkins R (1996) The blind watchmaker: why the evidence of evolution reveals a universe without design. Norton, New YorkGoogle Scholar
  31. Dretske FI (2000) Perception, knowledge, and belief: selected essays. Cambridge University Press, CambridgeGoogle Scholar
  32. Eklund SE, Taylor D, Kozlov E, Prokop A, Cliffel DE (2004) A microphysiometer for simultaneous measurement of changes in extracellular glucose, lactate, oxygen, and acidification rate. Anal Chem 76:519–527PubMedGoogle Scholar
  33. Elsasser WM (1998) Reflections on a theory of organisms: holism in biology. Johns Hopkins University Press, BaltimoreGoogle Scholar
  34. Endy D, Brent R (2001) Modelling cellular behaviour. Nature 409:391–395PubMedGoogle Scholar
  35. Enver T, Heyworth CM, Dexter TM (1998) Do stem cells play dice? Blood 92:348–351PubMedGoogle Scholar
  36. Ermentrout GB, Edelsteinkeshet L (1993) Cellular automata approaches to biological modeling. J Theor Biol 160:97–133PubMedGoogle Scholar
  37. Evans GA (2000) Designer science and the “omic” revolution. Nat Biotechnol 18:127PubMedGoogle Scholar
  38. Ferrell JE, Machleder EM (1998) The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280:895–898PubMedGoogle Scholar
  39. Fitzhugh R (1961) Impulses and physiological states in theoretical models of nerve membrane. Biophys J 1:445–466PubMedGoogle Scholar
  40. Freitas RA Jr (2002) The future of nanofabrication and molecular scale devices in nanomedicine. Stud Health Technol Inform 80:45–59PubMedGoogle Scholar
  41. Gardner TS, di Bernardo D, Lorenz D, Collins JJ (2003) Inferring genetic networks and identifying compound mode of action via expression profiling. Science 301:102–105PubMedGoogle Scholar
  42. Ge H, Walhout AJM, Vidal M (2003) Integrating ‘omic’ information: a bridge between genomics and systems biology. Trends Genet 19:551–560PubMedGoogle Scholar
  43. Gell-Mann M (1995) The quark and the jaguar: adventures in the simple and the complex. WH Freeman, New YorkGoogle Scholar
  44. Glass L (2001) Synchronization and rhythmic processes in physiology. Nature 410:277–284PubMedGoogle Scholar
  45. Gleick J (1988) Chaos: making a new science. Penguin, New YorkGoogle Scholar
  46. Goldberger AL, Amaral LAN, Hausdorff JM, Ivanov PC, Peng CK, Stanley HE (2002) Fractal dynamics in physiology: alterations with disease and aging. Proc Natl Acad Sci USA 99:2466–2472PubMedGoogle Scholar
  47. Goodwin BC (2001) How the leopard changed its spots: the evolution of complexity. Princeton University Press, PrincetonGoogle Scholar
  48. Goodwin BC, Kauffman S, Murray JD (1993) Is morphogenesis an intrinsically robust process? J Theor Biol 163:135–144PubMedGoogle Scholar
  49. Gould SJ (2002) The structure of evolutionary theory. Belknap Press of Harvard University Press, CambridgeGoogle Scholar
  50. Gould SJ, Lewontin RC (1979) The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc R Soc Lond B Biol Sci 205:581–598PubMedGoogle Scholar
  51. Graveley BR (2001) Alternative splicing: increasing diversity in the proteomic world. Trends Genet 17:100–107PubMedGoogle Scholar
  52. Gray RA, Jalife J, Panfilov AV, Baxter WT, Cabo C, Davidenko JM, Pertsov AM (1995) Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. Circulation 91:2454–2469PubMedGoogle Scholar
  53. Hall D, Minton AP (2003) Macromolecular crowding: qualitative and semiquantitative successes, quantitative challenges. Biochim Biophys Acta 1649:127–139PubMedGoogle Scholar
  54. Hasty J, Pradines J, Dolnik M, Collins JJ (2000) Noise-based switches and amplifiers for gene expression. Proc Natl Acad Sci USA 97:2075–2080PubMedGoogle Scholar
  55. Horgan J (1995) From complexity to perplexity. Sci Am 272:104–109Google Scholar
  56. Huang S (2004) Back to the biology in systems biology: what can we learn from biomolecular networks? Brief Funct Genomic Proteomic 2:279–297PubMedGoogle Scholar
  57. Huang S (2005) Multistability and multicellularity: cell fates as high-dimensional attractors of gene regulatory networks. In: Kriete A,Eils R (eds) Computational systems biology. Elsevier, Amsterdam, pp 293–326Google Scholar
  58. Huang S, Eichler G, Bar-Yam Y, Ingber DE (2005) Cell fates as high-dimensional attractor states of a complex gene regulatory network. Phys Rev Lett 94:128701PubMedGoogle Scholar
  59. Hume DA (2000) Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. Blood 96:2323–2328PubMedGoogle Scholar
  60. Ideker T, Galitski T, Hood L (2001) A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2:343–372PubMedGoogle Scholar
  61. Imhof LA, Fudenberg D, Nowak MA (2005) Evolutionary cycles of cooperation and defection. Proc Natl Acad Sci USA 102:10797–10800PubMedGoogle Scholar
  62. Ingber DE (1998) The architecture of life. Sci Am 278:48–57PubMedGoogle Scholar
  63. Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116:1157–1173PubMedGoogle Scholar
  64. Ivanov PC, Amaral LAN, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, Stanley HE (1999) Multifractality in human heartbeat dynamics. Nature 399:461–465PubMedGoogle Scholar
  65. Kaern M, Elston TC, Blake WJ, Collins JJ (2005) Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet 6:451–464PubMedGoogle Scholar
  66. Kauffman SA (1993) The origins of order: self-organization and selection in evolution. Oxford University Press, New YorkGoogle Scholar
  67. Kirschner M, Gerhart J, Mitchison T (2000) Molecular “vitalism”. Cell 100:79–88PubMedGoogle Scholar
  68. Kitano H, Oda K, Kimura T, Matsuoka Y, Csete M, Doyle J, Muramatsu M (2004) Metabolic syndrome and robustness tradeoffs. Diabetes 53 [Suppl 3]:S6–S15Google Scholar
  69. Klevecz RR, Bolen J, Forrest G, Murray DB (2004) A genomewide oscillation in transcription gates DNA replication and cell cycle. Proc Natl Acad Sci USA 101:1200–1205PubMedGoogle Scholar
  70. Kocer A, Walko M, Meijberg W, Feringa BL (2005) A light-actuated nanovalve derived from a channel protein. Science 309:755–758PubMedGoogle Scholar
  71. Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, Alon U (2004) Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet 36:147–150PubMedGoogle Scholar
  72. Langton CG (1997) Artificial life: an overview. MIT Press, CambridgeGoogle Scholar
  73. Laurent M, Kellershohn N (1999) Multistability: a major means of differentiation and evolution in biological systems. Trends Biochem Sci 24:418–422PubMedGoogle Scholar
  74. Le TT, Harlepp S, Guet CC, Dittmar K, Emonet T, Pan T, Cluzel P (2005) Real-time RNA profiling within a single bacterium. Proc Natl Acad Sci USA 102:9160–9164PubMedGoogle Scholar
  75. Levsky JM, Singer RH (2003) Gene expression and the myth of the average cell. Trends Cell Biol 13:4–6PubMedGoogle Scholar
  76. Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836–840PubMedGoogle Scholar
  77. Lewontin RC (2001) The triple helix: gene, organism, and environment. Harvard University Press, CambridgeGoogle Scholar
  78. Lowrey PL, Takahashi JS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5:407–441PubMedGoogle Scholar
  79. Lu JZ, Rosenzweig Z (2000) Nanoscale fluorescent sensors for intracellular analysis. Fresenius J Anal Chem 366:569–575PubMedGoogle Scholar
  80. Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R (2005) Formation of regulatory patterns during signal propagation in a mammalian cellular network. Science 309:1078–1083PubMedGoogle Scholar
  81. Mackey MC, Glass L (1977) Oscillation and chaos in physiological control systems. Science 197:287–288PubMedGoogle Scholar
  82. Mandelbrot BB (1982) The fractal geometry of nature. WH Freeman, San FranciscoGoogle Scholar
  83. Mangan S, Alon U (2003) Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA 100:11980–11985PubMedGoogle Scholar
  84. Marcotte EM (2001) The path not taken. Nat Biotechnol 19:626–627PubMedGoogle Scholar
  85. Marsh BJ, Mastronarde DN, Buttle KF, Howell KE, McIntosh JR (2001) Organellar relationships in the Golgi region of the pancreatic beta cell line, HIT-T15, visualized by high resolution electron tomography. Proc Natl Acad Sci USA 98:2399–2406PubMedGoogle Scholar
  86. Medina M (2005) Genomes, phylogeny, and evolutionary systems biology. Proc Natl Acad Sci USA 102 [Suppl 1]:6630–6635Google Scholar
  87. Meinhardt H (1996) Models of biological pattern formation: common mechanism in plant and animal development. Int J Dev Biol 40:123–134PubMedGoogle Scholar
  88. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298:824–827PubMedGoogle Scholar
  89. Morange M (2001) The misunderstood gene. Harvard University Press, CambridgeGoogle Scholar
  90. Murray JD (1993) Mathematical biology. Springer-Verlag, Heidelberg, Berlin, New YorkGoogle Scholar
  91. Nguyen TD, Tseng HR, Celestre PC, Flood AH, Liu Y, Stoddart JF, Zink JI (2005) A reversible molecular valve. Proc Natl Acad Sci USA 102:10029–10034PubMedGoogle Scholar
  92. Nicolis G, Prigogine I (1989) Exploring complexity: an introduction. WH Freeman, New YorkGoogle Scholar
  93. Ninfa AJ, Mayo AE (2004) Hysteresis vs. graded responses: the connections make all the difference. Science's STKE 2004:e20Google Scholar
  94. Noble D (2002) Modeling the heart—from genes to cells to the whole organ. Science 295:1678–1682PubMedGoogle Scholar
  95. Normile D (1999) Building working cells ‘in silico’. Science 284:80–81PubMedGoogle Scholar
  96. Okubo A (1986) Dynamical aspects of animal grouping: swarms, schools, flocks, and herds. Adv Biophys 22:1–94PubMedGoogle Scholar
  97. Ozbudak EM, Thattai M, Lim HN, Shraiman BI, van Oudenaarden A (2004) Multistability in the lactose utilization network of Escherichia coli. Nature 427:737–740PubMedGoogle Scholar
  98. Palsson E, Cox EC (1996) Origin and evolution of circular waves and spirals in Dictyostelium discoideum territories. Proc Natl Acad Sci USA 93:1151–1155PubMedGoogle Scholar
  99. Papin JA, Price ND, Wiback SJ, Fell DA, Palsson BO (2003) Metabolic pathways in the post-genome era. Trends Biochem Sci 28:250–258PubMedGoogle Scholar
  100. Pattee HH (1973) Hierarchy theory: the challenge of complex systems. G Braziller, New YorkGoogle Scholar
  101. Picht G (1969) Mut zur Utopie: die grossen Zukunftsaufgaben; zwölf Vorträge. R Piper, MünchenGoogle Scholar
  102. Pugh GE (1977) The biological origin of human values. Basic Books, New YorkGoogle Scholar
  103. Reik W, Dean W (2002) Back to the beginning. Nature 420:127PubMedGoogle Scholar
  104. Rocheleau JV, Walker GM, Head WS, McGuinness OP, Piston DW (2004) Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets. Proc Natl Acad Sci USA 101:12899–12903PubMedGoogle Scholar
  105. Rose SPR (2003) Lifelines: life beyond the gene. Oxford University Press, OxfordGoogle Scholar
  106. Rubin H (1990) On the nature of enduring modifications induced in cells and organisms. Am J Physiol 258:L19–L24PubMedGoogle Scholar
  107. Sachs K, Perez O, Pe'er D, Lauffenburger DA, Nolan GP (2005) Causal protein-signaling networks derived from multiparameter single-cell data. Science 308:523–529PubMedGoogle Scholar
  108. Sarpeshkar R (1998) Analog versus digital: extrapolating from electronics to neurobiology. Neural Comput 10:1601–1638PubMedGoogle Scholar
  109. Schmidt-Nielsen K (1984) Scaling: why is animal size so important. Cambridge University Press, New YorkGoogle Scholar
  110. Simon SM, Llinas RR (1985) Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release. Biophys J 48:485–498PubMedGoogle Scholar
  111. Sohrmann M, Peter M (2003) Polarizing without a C(l)ue. Trends Cell Biol 13:526–533PubMedGoogle Scholar
  112. Southan C (2004) Has the yo-yo stopped? An assessment of human protein-coding gene number. Proteomics 4:1712–1726PubMedGoogle Scholar
  113. Springel V, White SDM, Jenkins A, Frenk CS, Yoshida N, Gao L, Navarro J, Thacker R, Croton D, Helly J, Peacock JA, Cole S, Thomas P, Couchman H, Evrard A, Colberg J, Pearce F (2005) Simulations of the formation, evolution and clustering of galaxies and quasars. Nature 435:629–636PubMedGoogle Scholar
  114. Spudich JL, Koshland DE (1976) Non-genetic individuality: chance in the single cell. Nature 262:467–471PubMedGoogle Scholar
  115. Stelling J, Sauer U, Szallasi Z, Doyle FJ, Doyle J (2004) Robustness of cellular functions. Cell 118:675–685PubMedGoogle Scholar
  116. Stephanopoulos GN, Aristidou AA, Nielsen J (1998) Metabolic engineering: principles and methodologies. Academic Press, San DiegoGoogle Scholar
  117. Strogatz SH (2001) Exploring complex networks. Nature 410:268–276PubMedGoogle Scholar
  118. Strohman RC (1997) The coming Kuhnian revolution in biology. Nat Biotechnol 15:194–200PubMedGoogle Scholar
  119. Strohman RC (2000) Organization becomes cause in the matter. Nat Biotechnol 18:575–576PubMedGoogle Scholar
  120. Stuart JM, Segal E, Koller D, Kim SK (2003) A gene-coexpression network for global discovery of conserved genetic modules. Science 302:249–255PubMedGoogle Scholar
  121. Takahashi K, Arjunan SNV, Tomita M (2005) Space in systems biology of signaling pathways—towards intracellular molecular crowding in silico. FEBS Lett 579:1783–1788PubMedGoogle Scholar
  122. Tinbergen N (1952) Derived activities: their causation, biological significance, origin, and emancipation during evolution. Q Rev Biol 27:1–32PubMedGoogle Scholar
  123. Turing AM (1952) The chemical basis of morphogenesis. Philos Trans R Soc Lond B Biol Sci 237:37–72Google Scholar
  124. 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 15:221–231PubMedGoogle Scholar
  125. von Bertalanffy L (1969) General system theory; foundations, development, applications. G Braziller, New YorkGoogle Scholar
  126. Waddington CH (1956) Principles of embryology. Allen and Unwin, LondonGoogle Scholar
  127. Waldrop MM (1992) Complexity: the emerging science at the edge of order and chaos. Simon and Schuster, New YorkGoogle Scholar
  128. Webster G, Goodwin BC (1984) A structuralist approach to morphology. Riv Biol 77:503–531PubMedGoogle Scholar
  129. Whitesides GM (2003) The ‘right’ size in nanobiotechnology. Nat Biotechnol 21:1161–1165PubMedGoogle Scholar
  130. Whitfield ML, Sherlock G, Saldanha AJ, Murray JI, Ball CA, Alexander KE, Matese JC, Perou CM, Hurt MM, Brown PO, Botstein D (2002) Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13:1977–2000PubMedGoogle Scholar
  131. Wiener N (1965) Cybernetics: or control and communication in the animal and the machine. MIT Press, CambridgeGoogle Scholar
  132. Wikswo JP, Prokop A, Baudenbacher F, Cliffel D, Csukas B, Velkovsky M (2006) The engineering challenges of BioNEMS: the integration of microfluidics, and micro- and nanodevices, models, and external control for systems biology. IEE Proceedings Nanobiotechnology (in press)Google Scholar
  133. Wilders R, Jongsma HJ (1993) Beating irregularity of single pacemaker cells isolated from the rabbit sinoatrial node. Biophys J 65:2601–2613PubMedGoogle Scholar
  134. Wilson EO (1995) Naturalist. Warner Books, New YorkGoogle Scholar
  135. Wolfe MF, Goldberg R (2000) Rube Goldberg: inventions. Simon and Schuster, New YorkGoogle Scholar
  136. Wolfram S (2002) A new kind of science. Wolfram Media, ChampaignGoogle Scholar
  137. Wolpert L (1994) Do we understand development? Science 266:571–572PubMedGoogle Scholar
  138. Xiong W, Ferrell JE (2003) A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision. Nature 426:460–465PubMedGoogle Scholar
  139. Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T, Takumi T (2004) Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. BMC Mol Biol 5:18PubMedGoogle Scholar
  140. Yi TM, Huang Y, Simon MI, Doyle J (2000) Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci USA 97:4649–4653PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Surgery and Vascular Biology ProgramHarvard Medical SchoolBostonUSA
  2. 2.Vanderbilt Institute for Integrative Biosystems Research and Education, Departments of Biomedical Engineering, Molecular Physiology & Biophysics and Physics & AstronomyVanderbilt UniversityNashvilleUSA

Personalised recommendations