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

美国-匈牙利关于“细胞分裂周期的数学模型”的研究项目是由弗吉尼亚理工大学的John J.Tyson博士和布达佩斯技术大学的Bela Novak博士共同完成的。最近的分子研究已经揭示了四类蛋白质，它们显著参与了分裂控制机制。两种蛋白质(cdc2和细胞周期蛋白)结合形成异源二聚体(“有丝分裂促进因子”或MPF)，当被激活时，会触发所有重大的有丝分裂和细胞分裂事件。MPF的活性又由决定MPF磷酸化状态的蛋白激酶和蛋白磷酸酶控制。这个联合项目的目标是开发细胞分裂周期的数学模型，以便在控制机制的分子细节和对完整调控系统行为的经典观察之间建立安全可靠的联系。该模型将描述MPF活性通过磷酸化的调节，以及MPF的磷酸化状态如何由细胞的DNA与蛋白质的比例决定。这项研究应该产生一种数学工具来完善假设，并指导关于细胞生长和分裂的基本事件的推理。这项在细胞生物学和数学方面的研究通过使美国和匈牙利的顶尖专家能够将互补的人才结合在一起，并在相互感兴趣和能力很强的领域汇集研究资源，实现了推进科学的计划目标。

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.