Development and Validation of a Computational Model for Intra-Cellular Circadian Oscillators

摘要

Circadian rhythms are endogenous rhythms in physiology or behavior with a cycle length near 24 hours. Circadian rhythms are relevant to military activities because the ability of military personnel to maintain high level of cognitive performance and vigilance for long intervals is degraded by human factors, including fatigue, sleep loss and other circadian factors. Underlying circadian rhythmicity is a molecular feedback loop. This project developed mathematical models of the mammalian circadian oscillator. Our approach was to gather information on parameters needed for model development through biochemical experiments, develop mathematical models of the mammalian circadian oscillator, and experimentally test predictions from these models. We created a reduced molecular model, with the long-term objective of incorporating a molecular model into an existing model of the influence of light and rhythmicity on human performance. Our experimental and modeling efforts led to several publications and the contribution of software for numerous circadian models to BioSpice. Understanding of the circadian oscillatory mechanism has the potential for new strategies in resetting the circadian clock to promote alertness and to enhance physiological synchronization to new environments after transmeridian travel. Our development of detailed molecular models of the mammalian clock provides an important first step towards these objectives.