Multiscale Modeling of Circadian Rhythms

项目摘要/摘要 在这个项目中，我们将扩展一种新的建模方法，使模拟 耦合的化学反应，如在新陈代谢中发现的那些，更容易 落实和运用。新的方法依赖于群体行动动力学，并使 在大尺度上模拟生物现象要容易得多，因为(1)时间可以 被重新调整到适当的程度，以及(2)动力学方程是“伸缩的”-- 也就是说，可以折叠耦合反应的集合，并且只对概要反应进行建模 用这种方法。 我们将用这种新的方法来理解它的动力学行为和昼夜节律。 细胞的节律。昼夜节律在复杂的生物体中被发现，从 蓝藻对人类的影响，并代表着细胞调节的一个主要方面 大多数真核生物。这些节律控制着细胞行为的许多方面， 从在真菌中释放纤维素酶以降解环境中的纤维素到 人类细胞的动态。人体昼夜节律失调是新陈代谢的基础， 行为和认知障碍。 新的方法是基于物理学和统计学的最新发展 热力学涨落理论。在这些方法中，对相对时间进行建模- 可以证明，反应的依赖比对绝对反应进行建模要容易得多 时间到了。我们将不仅将这些方法应用于代谢的酶反应， 而且还连接到包含控制生物钟的生物钟的调节网络 细胞在24小时内的代谢。

Project Summary/Abstract In this project we will extend a new method of modeling that makes the simulation of coupled chemical reactions, such as those found in metabolism, much easier to implement and apply. The new approach relies upon mass action dynamics and makes modeling biological phenomena across large scales much easier because (1) time can be rescaled to an appropriate degree and (2) the dynamical equations are `telescopic' – that is, sets of coupled reactions can be collapsed and just summary reactions modeled with the approach. We will apply this new method to understand the dynamical behavior and circadian rhythms of cells. Circadian rhythms are found in organisms ranging in complexity from cyanobacteria to humans and represent a major aspect of cellular regulation in the majority of eukaryotes. These rhythms control many aspects of cellular behavior, ranging from the release of cellulases in fungi to degrade cellulose in the environment to the dynamics of human cells. Circadian dysfunction in humans underlies metabolic, behavioral, and cognitive disorders. The new approach is based on recent developments in physics, and in statistical thermodynamic fluctuation theories. In these approaches, modeling the relative time- dependence of reactions can be shown to be much easier than modeling the absolute time. We will apply these methods not only to the enzymatic reactions of metabolism, but also to the regulatory network that comprises the circadian clock which controls the metabolism of cells over a period of 24 hours.