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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Related Publication
  • A mathematical model for the intracellular circadian rhythm generator.
  • Scheper T, Klinkenberg D, Pennartz C, van Pelt J
  • The Journal of neuroscience : the official journal of the Society for Neuroscience , 1/ 1999 , Volume 19 , pages: 40-47
  • Oxford Brookes University, School for Computing and Math Science, Gipsy Lane Campus, OX3 0BP Headington Oxford, United Kingdom.
  • A mathematical model for the intracellular circadian rhythm generator has been studied, based on a negative feedback of protein products on the transcription rate of their genes. The study is an attempt at examining minimal but biologically realistic requirements for a negative molecular feedback loop involving considerably faster reactions, to produce (slow) circadian oscillations. The model included mRNA and protein production and degradation, along with a negative feedback of the proteins upon mRNA production. The protein production process was described solely by its total duration and a nonlinear term, whereas also the feedback included nonlinear interactions among protein molecules. This system was found to produce robust oscillations in protein and mRNA levels over a wide range of parameter values. Oscillations were slow, with periods much longer than the time constants of any of the individual system parameters. Circadian oscillations were obtained for realistic values of the parameters. The system was readily entrainable to external periodic perturbations. Two distinct classes of phase response curves were found, viz. with or without a time domain within the circadian cycle in which external perturbations fail to induce a phase shift ("dead zone"). The delay and nonlinearity in the protein production and the cooperativity in the negative feedback (Hill coefficient) were for this model found to be necessary and sufficient to generate robust circadian oscillations. The similarities between model outcomes and empirical findings establish that circadian rhythmicity at the cellular level can plausibly emerge from interactions among molecular systems which are not in themselves rhythmic.
Nicolas Le Novère

Metadata information

PubMed 9870936
Curation status
  • Model originally submitted by : Nicolas Le Novère
  • Submitted: 13-Sep-2005 14:31:01
  • Last Modified: 25-Feb-2015 13:35:10
  • Version: 2 public model Download this version
    • Submitted on: 25-Feb-2015 13:35:10
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Scheper1999_CircClock
  • Version: 1 public model Download this version
    • Submitted on: 13-Sep-2005 14:31:01
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of Scheper1999_CircClock
Curator's comment:
(added: 19 Oct 2006, 22:37:25, updated: 19 Oct 2006, 22:37:25)
Figure 2 bottom reproduced by xppaut 5.85