文章基本信息

标题：Toward Multi-Input Control: A Dual-Feedback Loop Model of the Mammalian Circadian Clock ⁎
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作者：Lindsey S. Brown ; Francis J. Doyle
期刊名称：IFAC PapersOnLine
印刷版ISSN：2405-8963
出版年度：2018
卷号：51
期号：19
页码：24-27
DOI：10.1016/j.ifacol.2018.09.022
语种：English
出版社：Elsevier
摘要：AbstractMany mathematical models have been used to describe the mammalian circadian clock, ranging from phase-only models to complex systems of differential equations. Here, we develop a 14 state model of the molecular clock, which provides sufficient detail to consider multi-input control. Assuming mass action and Michaelis-Menten kinetics, we derive a model of the transcription-translation feedback loops in the mammalian clock. Using a genetic algorithm, we fit the parameters of the model to capture the appropriate peak to trough ratios, relative abundances, and phase differences of the model species. We show that this in silico model captures much of the behavior that is observed in vitro under knockout conditions of different molecular species, validating our model. Thus, this model gives a simple but valid model of both feedback loops in the mammalian clock, providing the opportunity for enhanced control of both the phase and amplitude of the clock through multi-input control in a combination of small molecules which act on the species in both the positive and negative feedback loops.
关键词：KeywordsCircadian oscillatorbiological controlparameter identificationmodelslimit cycles