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

细胞分裂周期是活细胞复制其所有组分并将其在两个子细胞之间分裂的事件序列，因此每个子细胞都具有重复该过程所需的信息和机制。由于细胞周期是所有生物有机体生长、发育和繁殖的基础，因此分子生物学家对细胞周期进行了深入研究，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，调节机制是高度保守的，同源组分跨越从酵母到青蛙到人类的物种障碍发挥作用。这个控制系统的许多细节现在都是已知的，直观的方法无法解释这些分子成分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，首席研究员创建了数学工具来模拟控制系统，分析其属性，并将假设的机制与分裂细胞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，解决问题的环境（PSE）来建模细胞周期调控网络，从而将这些计算工具带给更广泛的理论和实验生物学家。当完全开发后，PSE将允许用户访问关于细胞周期基因和蛋白质的实验数据库，构建假设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，以便可以测试，改进和扩展潜在的机制假设。这个“孵化项目”将启动PSE的开发，以证明计算方法的可行性，从而为项目的全额资助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