Skip to main content
SpringerLink
Log in

Dimensions of systems biology

  • Chapter
  • First Online:
Reviews of Physiology Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology Biochemistry and Pharmacology ((REVIEWS,volume 157))

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.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Aebersold R (2005) Molecular systems biology: a new journal for a new biology? Mol Sys Biol 1:msb4100009 E1–E2

    Google Scholar 

  • Aebersold R, Hood LE, Watts JD (2000) Equipping scientists for the new biology. Nat Biotechnol 18:359

    PubMed  CAS  Google Scholar 

  • Albert R, Jeong H, Barabasi AL (2000) Error and attack tolerance of complex networks. Nature 406:378–382

    PubMed  CAS  Google Scholar 

  • Alon U (2003) Biological networks: the tinkerer as an engineer. Science 301:1866–1867

    PubMed  CAS  Google Scholar 

  • Alon U, Surette MG, Barkai N, Leibler S (1999) Robustness in bacterial chemotaxis. Nature 397:168–171

    PubMed  CAS  Google Scholar 

  • Anderson PW (1972) More is different: broken symmetry and the nature of the hierarchical structure of science. Science 177:393–396

    PubMed  CAS  Google Scholar 

  • Ashby WR (1964) An introduction to cybernetics. Routledge, Kegan and Paul, London

    Google Scholar 

  • Autumn K, Ryan MJ, Wake DB (2002) Integrating historical and mechanistic biology enhances the study of adaptation. Q Rev Biol 77:383–408

    PubMed  Google Scholar 

  • Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004) Bacterial persistence as a phenotypic switch. Science 305:1622–1625

    PubMed  CAS  Google Scholar 

  • Ball P (2001) The self-made tapestry: pattern formation in nature. Oxford University Press, Oxford

    Google Scholar 

  • Bar-Yam Y (1997) Dynamics of complex systems. Perseus Books, Reading

    Google Scholar 

  • Bar-Yam Y (2004) Multiscale variety in complex systems. Complexity 9:37–45

    Google Scholar 

  • Barabasi AL, Albert R (1999) Emergence of scaling in random networks. Science 286:509–512

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Barkai N, Leibler S (2000) Circadian clocks limited by noise. Nature 403:267–268

    PubMed  CAS  Google Scholar 

  • Blackett PMS (1963) Memories of Rutherford. In: Birks JB (ed) Rutherford at Manchester. Benjamin, New York, p 108

    Google Scholar 

  • Bassingthwaighte JB, Liebovitch LS, West BJ (1994) Fractal physiology. Oxford University Press, New York

    Google Scholar 

  • Braich RS, Chelyapov N, Johnson C, Rothemund PWK, Adleman L (2002) Solution of a 20-variable 3-SAT problem on a DNA computer. Science 296:499–502

    PubMed  CAS  Google Scholar 

  • Bray D (1997) Reductionism for biochemists: how to survive the protein jungle. Trends Biochem Sci 22:325–326

    PubMed  CAS  Google Scholar 

  • Brent R (2000) Genomic biology. Cell 100:169–183

    PubMed  CAS  Google Scholar 

  • 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 357:619–626

    PubMed  Google Scholar 

  • Carlson JM, Doyle J (2002) Complexity and robustness. Proc Natl Acad Sci USA 99:2538–2545

    PubMed  Google Scholar 

  • Cauwenberghs G (1995) A micropower CMOS algorithmic A/D/A converter. IEEE T Circuits Syst I 42:913–919

    Google Scholar 

  • Cherry EM, Greenside HS, Henriquez CS (2000) A space-time adaptive method for simulating complex cardiac dynamics. Phys Rev Lett 84:1343–1346

    PubMed  CAS  Google Scholar 

  • Corning PA (2002) The re-emergence of “emergence”: a venerable concept in search of a theory. Complexity 7:18–30

    Google Scholar 

  • Cross SS (1997) Fractals in pathology. J Pathol 182:1–8

    PubMed  CAS  Google Scholar 

  • 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 427:344–347

    PubMed  CAS  Google Scholar 

  • D'haeseleer P, Liang SD, Somogyi R (2000) Genetic network inference: from co-expression clustering to reverse engineering. Bioinformatics 16:707–726

    PubMed  Google Scholar 

  • 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 295:1669–1678

    PubMed  CAS  Google Scholar 

  • Dawkins R (1996) The blind watchmaker: why the evidence of evolution reveals a universe without design. Norton, New York

    Google Scholar 

  • Dretske FI (2000) Perception, knowledge, and belief: selected essays. Cambridge University Press, Cambridge

    Google Scholar 

  • 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 76:519–527

    PubMed  CAS  Google Scholar 

  • Elsasser WM (1998) Reflections on a theory of organisms: holism in biology. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Endy D, Brent R (2001) Modelling cellular behaviour. Nature 409:391–395

    PubMed  CAS  Google Scholar 

  • Enver T, Heyworth CM, Dexter TM (1998) Do stem cells play dice? Blood 92:348–351

    PubMed  CAS  Google Scholar 

  • Ermentrout GB, Edelsteinkeshet L (1993) Cellular automata approaches to biological modeling. J Theor Biol 160:97–133

    PubMed  CAS  Google Scholar 

  • Evans GA (2000) Designer science and the “omic” revolution. Nat Biotechnol 18:127

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Fitzhugh R (1961) Impulses and physiological states in theoretical models of nerve membrane. Biophys J 1:445–466

    PubMed  CAS  Google Scholar 

  • Freitas RA Jr (2002) The future of nanofabrication and molecular scale devices in nanomedicine. Stud Health Technol Inform 80:45–59

    PubMed  Google Scholar 

  • Gardner TS, di Bernardo D, Lorenz D, Collins JJ (2003) Inferring genetic networks and identifying compound mode of action via expression profiling. Science 301:102–105

    PubMed  CAS  Google Scholar 

  • Ge H, Walhout AJM, Vidal M (2003) Integrating ‘omic’ information: a bridge between genomics and systems biology. Trends Genet 19:551–560

    PubMed  CAS  Google Scholar 

  • Gell-Mann M (1995) The quark and the jaguar: adventures in the simple and the complex. WH Freeman, New York

    Google Scholar 

  • Glass L (2001) Synchronization and rhythmic processes in physiology. Nature 410:277–284

    PubMed  CAS  Google Scholar 

  • Gleick J (1988) Chaos: making a new science. Penguin, New York

    Google Scholar 

  • 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 99:2466–2472

    PubMed  Google Scholar 

  • Goodwin BC (2001) How the leopard changed its spots: the evolution of complexity. Princeton University Press, Princeton

    Google Scholar 

  • Goodwin BC, Kauffman S, Murray JD (1993) Is morphogenesis an intrinsically robust process? J Theor Biol 163:135–144

    PubMed  CAS  Google Scholar 

  • Gould SJ (2002) The structure of evolutionary theory. Belknap Press of Harvard University Press, Cambridge

    Google Scholar 

  • 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 205:581–598

    PubMed  CAS  Google Scholar 

  • Graveley BR (2001) Alternative splicing: increasing diversity in the proteomic world. Trends Genet 17:100–107

    PubMed  CAS  Google Scholar 

  • 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 91:2454–2469

    PubMed  CAS  Google Scholar 

  • Hall D, Minton AP (2003) Macromolecular crowding: qualitative and semiquantitative successes, quantitative challenges. Biochim Biophys Acta 1649:127–139

    PubMed  CAS  Google Scholar 

  • Hasty J, Pradines J, Dolnik M, Collins JJ (2000) Noise-based switches and amplifiers for gene expression. Proc Natl Acad Sci USA 97:2075–2080

    PubMed  CAS  Google Scholar 

  • Horgan J (1995) From complexity to perplexity. Sci Am 272:104–109

    Google Scholar 

  • Huang S (2004) Back to the biology in systems biology: what can we learn from biomolecular networks? Brief Funct Genomic Proteomic 2:279–297

    PubMed  CAS  Google Scholar 

  • 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 293–326

    Google Scholar 

  • 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 94:128701

    PubMed  Google Scholar 

  • Hume DA (2000) Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. Blood 96:2323–2328

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Imhof LA, Fudenberg D, Nowak MA (2005) Evolutionary cycles of cooperation and defection. Proc Natl Acad Sci USA 102:10797–10800

    PubMed  CAS  Google Scholar 

  • Ingber DE (1998) The architecture of life. Sci Am 278:48–57

    PubMed  CAS  Google Scholar 

  • Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116:1157–1173

    PubMed  CAS  Google Scholar 

  • Ivanov PC, Amaral LAN, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, Stanley HE (1999) Multifractality in human heartbeat dynamics. Nature 399:461–465

    PubMed  CAS  Google Scholar 

  • Kaern M, Elston TC, Blake WJ, Collins JJ (2005) Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet 6:451–464

    PubMed  CAS  Google Scholar 

  • Kauffman SA (1993) The origins of order: self-organization and selection in evolution. Oxford University Press, New York

    Google Scholar 

  • Kirschner M, Gerhart J, Mitchison T (2000) Molecular “vitalism”. Cell 100:79–88

    PubMed  CAS  Google Scholar 

  • 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–S15

    Google Scholar 

  • 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 101:1200–1205

    PubMed  CAS  Google Scholar 

  • Kocer A, Walko M, Meijberg W, Feringa BL (2005) A light-actuated nanovalve derived from a channel protein. Science 309:755–758

    PubMed  CAS  Google Scholar 

  • 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 36:147–150

    PubMed  CAS  Google Scholar 

  • Langton CG (1997) Artificial life: an overview. MIT Press, Cambridge

    Google Scholar 

  • Laurent M, Kellershohn N (1999) Multistability: a major means of differentiation and evolution in biological systems. Trends Biochem Sci 24:418–422

    PubMed  CAS  Google Scholar 

  • 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 102:9160–9164

    PubMed  CAS  Google Scholar 

  • Levsky JM, Singer RH (2003) Gene expression and the myth of the average cell. Trends Cell Biol 13:4–6

    PubMed  CAS  Google Scholar 

  • Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836–840

    PubMed  CAS  Google Scholar 

  • Lewontin RC (2001) The triple helix: gene, organism, and environment. Harvard University Press, Cambridge

    Google Scholar 

  • Lowrey PL, Takahashi JS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5:407–441

    PubMed  CAS  Google Scholar 

  • Lu JZ, Rosenzweig Z (2000) Nanoscale fluorescent sensors for intracellular analysis. Fresenius J Anal Chem 366:569–575

    PubMed  CAS  Google Scholar 

  • 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 309:1078–1083

    PubMed  Google Scholar 

  • Mackey MC, Glass L (1977) Oscillation and chaos in physiological control systems. Science 197:287–288

    PubMed  CAS  Google Scholar 

  • Mandelbrot BB (1982) The fractal geometry of nature. WH Freeman, San Francisco

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Marcotte EM (2001) The path not taken. Nat Biotechnol 19:626–627

    PubMed  CAS  Google Scholar 

  • 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 98:2399–2406

    PubMed  CAS  Google Scholar 

  • Medina M (2005) Genomes, phylogeny, and evolutionary systems biology. Proc Natl Acad Sci USA 102 [Suppl 1]:6630–6635

    Google Scholar 

  • Meinhardt H (1996) Models of biological pattern formation: common mechanism in plant and animal development. Int J Dev Biol 40:123–134

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Morange M (2001) The misunderstood gene. Harvard University Press, Cambridge

    Google Scholar 

  • Murray JD (1993) Mathematical biology. Springer-Verlag, Heidelberg, Berlin, New York

    Google Scholar 

  • Nguyen TD, Tseng HR, Celestre PC, Flood AH, Liu Y, Stoddart JF, Zink JI (2005) A reversible molecular valve. Proc Natl Acad Sci USA 102:10029–10034

    PubMed  CAS  Google Scholar 

  • Nicolis G, Prigogine I (1989) Exploring complexity: an introduction. WH Freeman, New York

    Google Scholar 

  • Ninfa AJ, Mayo AE (2004) Hysteresis vs. graded responses: the connections make all the difference. Science's STKE 2004:e20

    Google Scholar 

  • Noble D (2002) Modeling the heart—from genes to cells to the whole organ. Science 295:1678–1682

    PubMed  CAS  Google Scholar 

  • Normile D (1999) Building working cells ‘in silico’. Science 284:80–81

    PubMed  CAS  Google Scholar 

  • Okubo A (1986) Dynamical aspects of animal grouping: swarms, schools, flocks, and herds. Adv Biophys 22:1–94

    PubMed  CAS  Google Scholar 

  • Ozbudak EM, Thattai M, Lim HN, Shraiman BI, van Oudenaarden A (2004) Multistability in the lactose utilization network of Escherichia coli. Nature 427:737–740

    PubMed  CAS  Google Scholar 

  • Palsson E, Cox EC (1996) Origin and evolution of circular waves and spirals in Dictyostelium discoideum territories. Proc Natl Acad Sci USA 93:1151–1155

    PubMed  CAS  Google Scholar 

  • Papin JA, Price ND, Wiback SJ, Fell DA, Palsson BO (2003) Metabolic pathways in the post-genome era. Trends Biochem Sci 28:250–258

    PubMed  CAS  Google Scholar 

  • Pattee HH (1973) Hierarchy theory: the challenge of complex systems. G Braziller, New York

    Google Scholar 

  • Picht G (1969) Mut zur Utopie: die grossen Zukunftsaufgaben; zwölf Vorträge. R Piper, München

    Google Scholar 

  • Pugh GE (1977) The biological origin of human values. Basic Books, New York

    Google Scholar 

  • Reik W, Dean W (2002) Back to the beginning. Nature 420:127

    PubMed  CAS  Google Scholar 

  • 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 101:12899–12903

    PubMed  CAS  Google Scholar 

  • Rose SPR (2003) Lifelines: life beyond the gene. Oxford University Press, Oxford

    Google Scholar 

  • Rubin H (1990) On the nature of enduring modifications induced in cells and organisms. Am J Physiol 258:L19–L24

    PubMed  CAS  Google Scholar 

  • Sachs K, Perez O, Pe'er D, Lauffenburger DA, Nolan GP (2005) Causal protein-signaling networks derived from multiparameter single-cell data. Science 308:523–529

    PubMed  CAS  Google Scholar 

  • Sarpeshkar R (1998) Analog versus digital: extrapolating from electronics to neurobiology. Neural Comput 10:1601–1638

    PubMed  CAS  Google Scholar 

  • Schmidt-Nielsen K (1984) Scaling: why is animal size so important. Cambridge University Press, New York

    Google Scholar 

  • Simon SM, Llinas RR (1985) Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release. Biophys J 48:485–498

    PubMed  CAS  Google Scholar 

  • Sohrmann M, Peter M (2003) Polarizing without a C(l)ue. Trends Cell Biol 13:526–533

    PubMed  CAS  Google Scholar 

  • Southan C (2004) Has the yo-yo stopped? An assessment of human protein-coding gene number. Proteomics 4:1712–1726

    PubMed  CAS  Google Scholar 

  • 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 435:629–636

    PubMed  CAS  Google Scholar 

  • Spudich JL, Koshland DE (1976) Non-genetic individuality: chance in the single cell. Nature 262:467–471

    PubMed  CAS  Google Scholar 

  • Stelling J, Sauer U, Szallasi Z, Doyle FJ, Doyle J (2004) Robustness of cellular functions. Cell 118:675–685

    PubMed  CAS  Google Scholar 

  • Stephanopoulos GN, Aristidou AA, Nielsen J (1998) Metabolic engineering: principles and methodologies. Academic Press, San Diego

    Google Scholar 

  • Strogatz SH (2001) Exploring complex networks. Nature 410:268–276

    PubMed  CAS  Google Scholar 

  • Strohman RC (1997) The coming Kuhnian revolution in biology. Nat Biotechnol 15:194–200

    PubMed  CAS  Google Scholar 

  • Strohman RC (2000) Organization becomes cause in the matter. Nat Biotechnol 18:575–576

    PubMed  CAS  Google Scholar 

  • Stuart JM, Segal E, Koller D, Kim SK (2003) A gene-coexpression network for global discovery of conserved genetic modules. Science 302:249–255

    PubMed  CAS  Google Scholar 

  • Takahashi K, Arjunan SNV, Tomita M (2005) Space in systems biology of signaling pathways—towards intracellular molecular crowding in silico. FEBS Lett 579:1783–1788

    PubMed  CAS  Google Scholar 

  • Tinbergen N (1952) Derived activities: their causation, biological significance, origin, and emancipation during evolution. Q Rev Biol 27:1–32

    PubMed  CAS  Google Scholar 

  • Turing AM (1952) The chemical basis of morphogenesis. Philos Trans R Soc Lond B Biol Sci 237:37–72

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • von Bertalanffy L (1969) General system theory; foundations, development, applications. G Braziller, New York

    Google Scholar 

  • Waddington CH (1956) Principles of embryology. Allen and Unwin, London

    Google Scholar 

  • Waldrop MM (1992) Complexity: the emerging science at the edge of order and chaos. Simon and Schuster, New York

    Google Scholar 

  • Webster G, Goodwin BC (1984) A structuralist approach to morphology. Riv Biol 77:503–531

    PubMed  CAS  Google Scholar 

  • Whitesides GM (2003) The ‘right’ size in nanobiotechnology. Nat Biotechnol 21:1161–1165

    PubMed  CAS  Google Scholar 

  • 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 13:1977–2000

    PubMed  CAS  Google Scholar 

  • Wiener N (1965) Cybernetics: or control and communication in the animal and the machine. MIT Press, Cambridge

    Google Scholar 

  • 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 

  • Wilders R, Jongsma HJ (1993) Beating irregularity of single pacemaker cells isolated from the rabbit sinoatrial node. Biophys J 65:2601–2613

    PubMed  CAS  Google Scholar 

  • Wilson EO (1995) Naturalist. Warner Books, New York

    Google Scholar 

  • Wolfe MF, Goldberg R (2000) Rube Goldberg: inventions. Simon and Schuster, New York

    Google Scholar 

  • Wolfram S (2002) A new kind of science. Wolfram Media, Champaign

    Google Scholar 

  • Wolpert L (1994) Do we understand development? Science 266:571–572

    PubMed  CAS  Google Scholar 

  • Xiong W, Ferrell JE (2003) A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision. Nature 426:460–465

    PubMed  CAS  Google Scholar 

  • 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 5:18

    PubMed  Google Scholar 

  • Yi TM, Huang Y, Simon MI, Doyle J (2000) Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci USA 97:4649–4653

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We are deeply indebted to the many colleagues and friends who, through their publications, conversations, and presentations, have helped educate us about many aspects of systems biology and have critiqued our views. We apologize to those whose work is not explicitly mentioned. A list of all original references would have been irresponsibly long. Our citations also do not meet the standard of a disciplined historian of science. Rather than consistently reflecting the originators of an idea, the citations were chosen to be most practical and instructive for readers who seek further reading on a subject. We are indebted to Allison Price and Don Berry for their unflagging editorial assistance with this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery and Vascular Biology Program, Harvard Medical School, Karp 11-212, Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    S. Huang

  2. Vanderbilt Institute for Integrative Biosystems Research and Education, Departments of Biomedical Engineering, Molecular Physiology & Biophysics and Physics & Astronomy, Vanderbilt University, VU Station B 351807, Nashville, TN, 37235, USA

    J. Wikswo

Authors
  1. S. Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Wikswo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Huang .

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag

About this chapter

Cite this chapter

Huang, S., Wikswo, J. (2006). Dimensions of systems biology. In: Reviews of Physiology Biochemistry and Pharmacology. Reviews of Physiology Biochemistry and Pharmacology, vol 157. Springer, Berlin, Heidelberg. https://doi.org/10.1007/112_0602

Download citation

  • DOI: https://doi.org/10.1007/112_0602

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-39688-8

  • Online ISBN: 978-3-540-39689-5

Publish with us

Policies and ethics

Search

Navigation