Dr Didier Gonze
Research AssistantUnité de Chronobiologie Théorique
email: dgonze |
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We proposed and analysed mathematical models based on the negative autoregulation of the frq gene that underlies the Neurospora circadian rhythm. The model accounts for the occurrence of these oscillations in constant environmental conditions (e.g. constant darkness), for entrainment of these rhythms by light-dark cycles, for their phase-shifting induced by light pulses and for temperature compensation.
In an experimental study, Ouyang et al. (1998) have shown that, in direct competition, cyanobacterial strains whose circadian clocks have free-running periods (FRPs) which match the period of an imposed light/dark (LD) cycle exclude strains whose FRPs are out of resonance with the LD cycle. These differences in competitive fitness are observed despite the lack of measurable differences in monoculture growth rates between the strains. We showed that these experimental results are consistent with a mathematical model in which cells rhythmically produce a metabolic inhibitor to which they display a sensitivity modulated by their circadian rhythm. This study is made in collaboration with Marc Roussel (Lethbridge Univ., Canada).
Intrinsic molecular fluctuations may result from the small numbers of protein and mRNA molecules involved in the oscillations at the cellular level. In these conditions, it becomes necessary to resort to stochastic simulations to assess the influence of molecular noise on circadian oscillations. We addressed the effect of molecular noise by considering the stochastic version of the deterministic models and by applying specific algorithms to simulate these stochastic models.
The suprachiasmatic nuclei (SCN) of the hypothalamus is known as the center of the circadian clock. It contains the pacemaker which control peripheral oscillations present in other parts of the brain as well as in peripheral tissues. The SCN structure is highly heterogeneous. A fundamental issue with regard to the organization of the circadian system is how the SCN achieve a coherent output while the individual cellular oscillators express a wide range of phases and periods and how this system integrates light signals. In order of getting more understanding of this organisation, we study the dynamic properties of coupled circadian oscillators. This study is made in collaboration with Prof. H. Herzel, C. Waltermann and S. Bernard (ITB, Humboldt Univ. Berlin, Germany).
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