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Development and Validation of Computational Models for Mammalian Circadian Oscillators

机译:哺乳动物昼夜节律振荡器的计算模型的开发和验证

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摘要

Circadian rhythms are endogenous rhythms with a cycle length of approximately 24 h. Rhythmic production of specific proteins within pacemaker structures is the basis for these physiological and behavioral rhythms. Prior work on mathematical modeling of molecular circadian oscillators has focused on the fruit fly, Drosophila melanogaster. Recently, great advances have been made in our understanding of the molecular basis of circadian rhythms in mammals. Mathematical models of the mammalian circadian oscillator are needed to piece together diverse data, predict experimental results, and help us understand the clock as a whole. Our objectives are to develop mathematical models of the mammalian circadian oscillator, generate and test predictions from these models, gather information on the parameters needed for model development, integrate the molecular model with an existing model of the influence of light and rhythmicity on human performance, and make models available in BioSpice so that they can be easily used by the general community. Two new mammalian models have been developed, and experimental data are summarized. These studies have the potential to lead to new strategies for resetting the circadian clock. Manipulations of the circadian clock can be used to optimize performance by promoting alertness and physiological synchronization.
机译:昼夜节律是内源性节律,周期长度约为24小时。起搏器结构内特定蛋白质的节律性产生是这些生理和行为节律的基础。分子昼夜节律振荡器的数学建模的先前工作集中在果蝇果蝇(Drosophila melanogaster)。最近,在我们对哺乳动物昼夜节律的分子基础的理解上取得了很大的进步。需要哺乳动物昼夜节律振荡器的数学模型来整理各种数据,预测实验结果,并帮助我们整体了解时钟。我们的目标是开发哺乳动物昼夜节律振荡器的数学模型,从这些模型生成和测试预测,收集有关模型开发所需参数的信息,将分子模型与现有的光照和节律性对人类行为影响的模型进行整合,并在BioSpice中提供模型,以便普通社区可以轻松使用它们。已经开发了两种新的哺乳动物模型,并总结了实验数据。这些研究有可能导致重新设定生物钟的新策略。通过促进机敏性和生理同步,可以使用生物钟的时钟来优化性能。

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