Abstract
In the 1990s circadian rhythm researchers made enormous progress in identifying the components and operations within the responsible mechanism in various species using the tools of molecular biology. In the past decade it has proven essential to supplement these with the tools of systems biology both to identify additional components but especially to understand how the mechanism can generate circadian phenomena. This has proven especially important since research has shown that individual neurons in the mammalian mechanism are highly variable and that the way they are organized in networks is crucial to generating regular circadian behavior.
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Notes
- 1.
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In his analog simulations Goodwin reported oscillatory behavior with values as low as 2 or 3 for the Hill coefficient, but shortly afterward Griffith found in digital simulations that undamped oscillations would only occur with values greater than 9, generally recognized as biologically unrealistic: see J. S. Griffith, “Mathematics of Cellular Control Processes I. Negative Feedback to One Gene”, in: Journal of Theoretical Biology 20, 2, 1968, pp. 202-208. Accordingly, he concluded that negative feedback with a single gene product operating on a gene could never “give rise in practice to undamped oscillations in the concentrations of cellular constituents.” Subsequently models, such as those of Goldbeter (discussed below) employ additional nonlinearities elsewhere in the model (e.g., involving the degradation of various components) and so are able to use values of the Hill coefficient that are more biologically realistic.
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See Bechtel, op. cit. and Bechtel and Abrahamsen, op. cit.
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Bechtel, W. (2013). From Molecules to Networks: Adoption of Systems Approaches in Circadian Rhythm Research. In: Andersen, H., Dieks, D., Gonzalez, W., Uebel, T., Wheeler, G. (eds) New Challenges to Philosophy of Science. The Philosophy of Science in a European Perspective, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5845-2_17
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