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From circadian clock mechanism to sleep disorders and jet lag: Insights from a computational approach

Albert Goldbeter, Universit茅 Libre de Bruxelles
Tuesday March 9, 12-1pm
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Abstract: We present ten insights gained from a computational approach to the molecular mechanism of the mammalian circadian clock. These insights pertain to (1) the conditions in which circadian rhythms occur spontaneously, with a period close to 24h, in the form of limit cycle oscillations, (2) circadian clock entrainment by the light-dark (LD) cycle, (3) the dynamical bases of sleep-wake cycle disorders related to the circadian-clock, and (4) jet lag. The sleep disorders include the familial advanced sleep phase syndrome (FASPS), the delayed sleep phase syndrome (DSPS), and the non-24h sleep-wake cycle syndrome, in which the phase of the circadian clock drifts in the course of time. In regard to jet lag, the computational approach accounts for two modes of re-entrainment observed after a phase shift in the LD cycle and reveals conditions in which the resynchronization of the circadian clock may take a very long time. Repetitive perturbations of the circadian clock due to chronic jet lag may lead to irregular or even chaotic oscillations.

References

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J.-C. Leloup, A. Goldbeter (2004) Modeling the mammalian circadian clock: Sensitivity analysis and multiplicity of oscillatory mechanisms, J. Theor. Biol. 230, 541-562.

J.-C. Leloup, A. Goldbeter, (2008) Modeling the circadian clock : From molecular mechanism to physiological disorders. BioEssays 30, 590-600.

J.-C. Leloup, A. Goldbeter (2013) Critical phase shifts slow down circadian clock recovery: Implications for jet lag, J. Theor. Biol. 333, 47-57.

A. Goldbeter, J.-C. Leloup, (2021) From circadian clock mechanism to sleep disorders and jet lag: Insights from a computational approach, Biochemical Pharmacology, in press.