A model for the Neurospora circadian clock.
Circadian clocks are important biological oscillators that generally involve two feedback loops. Here, we propose a new model for the Neurospora crassa circadian clock. First, we model its main negative feedback loop, including only experimentally well-documented reactions, the transcriptional activation of frequency (frq) by the white-collar complex (WCC), and the post-transcriptional dimerization of FRQ with WCC. This main loop is sufficient for oscillations and a similar one lies at the core of almost all known circadian clocks. Second, the model is refined to include the less characterized enhancement of white-collar 1 (WC-1) protein synthesis by FRQ, the positive second feedback loop. Numerical testing of different hypotheses led us to propose that the synthesis of WC-1 is enhanced by FRQ monomers and repressed by FRQ dimers. We demonstrate that this second loop contributes significantly to the robustness of the oscillator period against parameter variation. A phase response curve to light pulses is also computed and agrees well with experiments. On a general level, our results show that explicit time delays are not required for sustained oscillations but that it is crucial to take into account mRNA dynamics and protein-protein interactions.
François
Paul
P
Laboratoire de Physique Statistique, Centre National de la Recherche Scientifique, UMR 8550, Ecole Normale Supérieure, Paris 75231, France. francois@tournesol.ps.ens.fr
D001683:Biological Clocks; D001703:Biophysics / Q000379:methods; D002940:Circadian Rhythm; D003720:Densitometry; D019281:Dimerization; D025461:Feedback, Physiological; D046911:Macromolecular Substances / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D008962:Models, Theoretical; D009492:Neurospora crassa / Q000378:metabolism / Q000502:physiology*; D009991:Oscillometry; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic
D046911:Macromolecular Substances; D012333:RNA, Messenger