U.S.-Hungary Cooperative Research on Mathematical Models of the Cell Division Cycle

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This U.S.-Hungary research project on "Mathematical Models of the Cell Division Cycle" is between Dr. John J. Tyson of Virginia Polytechnic Institute & State University, and Dr. Bela Novak of the Technical University, Budapest. Recent molecular studies have revealed four classes of proteins that participate prominently in the division control mechanism. Two proteins (cdc2 and cyclin) combine to form a heterodimer ("mitosis promoting factor," or MPF) that, when activated, triggers all the major events of mitosis and cell division. The activity of MPF is, in turn, controlled by protein kinases and protein phosphatases that determine the phosphorylation state of MPF. The goal of this joint project is to develop mathematical models of the cell division cycle, in order to build secure, reliable connections between molecular details of the control mechanism and classical observations of the behavior of the intact regulatory system. The model will describe the regulation of the MPF activity by phosphorylation, and how the phosphorylation state of MPF is determined by the DNA-to-protein ratio of the cell. The research should yield a mathematical tool to refine assumptions and guide reasoning about the essential events of cell growth and division. This research in cell biology and mathematics fulfills the program objective of advancing science by enabling leading experts in the United States and Hungary to combine complementary talents and pool research resources in areas of strong mutual interest and competence.