BIOCOMPLEXITY--INCUBATION ACTIVITY: A Collaborative Problem Solving Environment for Computational Modeling of Eukaryotic Cell Cycle Controls

细胞分裂周期是一系列事件，一个活细胞复制其所有成分，并将它们分裂到两个子细胞之间，以便每个子细胞拥有重复这一过程所需的信息和机制。由于细胞周期是所有生物生长、发育和繁殖的基础，细胞周期受到分子生物学家的密切研究，他们最近发现了控制细胞分裂的生化网络的许多细节。在真核细胞(植物、动物、真菌)中，调控机制是高度保守的，同源成分跨物种屏障发挥作用，从酵母到青蛙再到人类。这个控制系统的许多细节现已为人所知，直观的方法无法解释这些分子组成之间的复杂相互作用。迫切需要新的计算方法来描述复杂的基因调控系统。为此，首席调查员创建了数学工具来对控制系统进行建模，分析其属性，并将假设的机制与细胞分裂的实际行为进行比较。这个项目的目的是通过开发一个基于网络的、协作的、用于建模细胞周期调控网络的问题解决环境(PSE)，将这些计算工具带给更广泛的理论和实验生物学家。完全开发后，PSE将允许用户访问细胞周期基因和蛋白质的实验数据库，构建假想的控制机制并通过数值模拟探索其特性，并将模型行为与观察到的细胞特性进行比较，以便对潜在的机制假说进行测试、改进和扩展。这一“孵化项目”将启动PSE的开发，以证明计算方法的可行性，从而为该项目的全额供资提供令人信服的理由。

The cell division cycle is the sequence of events whereby a living cell replicates all its components and divides them between two daughter cells, so that each daughter has the information and machinery necessary to repeat the process. Because it underlies the growth, development and reproduction of all biological organisms, the cell cycle is intensely studied by molecular biologists, who have recently uncovered many details of the biochemical network controlling cell division. Among eukaryotic cells (plants, animals, fungi), the regulatory mechanism is highly conserved, with homologous components functioning across species barriers from yeast to frogs to humans. So many details of this control system are now known that intuitive methods cannot explicate the complex interactions among these molecular components. New computational methods to describe complex genetic regulatory systems are desperately needed. For this reason, the Principal Investigator has created mathematical tools to model the control system, analyze its properties, and compare hypothetical mechanisms to the actual behavior of dividing cells. The purpose of this project is to bring these computational tools to a wider audience of theoretical and experimental biologists by developing a web-based, collaborative, problem-solving environment (PSE) for modeling cell-cycle regulatory networks. When fully developed, the PSE will allow users to access experimental databases on cell cycle genes and proteins, to construct hypothetical control mechanisms and explore their properties by numerical simulation, and to compare model behavior with the observed properties of cells, so that the underlying mechanistic hypotheses can be tested, refined and expanded. This "incubation project" will initiate the development of the PSE, in order to demonstrate the feasibility of the computational method that will in turn make a convincing case for full funding of the project