A model for the Neurospora circadian clock

¹ Ecole Normale Supérieure

^* To whom correspondence should be addressed. E-mail: francois{at}tournesol.lps.ens.fr.

Submitted on October 4, 2004
Revised on October 31, 2004
Accepted on 28 December 2004

	Abstract

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 itsmain 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 (WC1) 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.

Key Words: Neurospora, circadian clocks, genetic oscillators, modeling

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