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

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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