Mathematical Models of the Cell Division Cycle

细胞分裂周期的数学模型

• 批准号: 9207160
• 负责人: John Tyson
• 金额: $ 16.54万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-15 至 1997-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9207160&HistoricalAwards=false
• 关键词: Mathematical; Models; Cell; Division; Cycle

The cell division cycle is the periodic repetition of certain events--DNA synthesis, mitosis, and cytokinesis--that transform a single cell into two daughter cells. Cell division must be coordinated to overall cell growth; otherwise, cells could become arbitrarily large or vanishingly small. By observing how cells respond to perturbations of the division cycle, cell biologists discovered that the DNA-to-protein ratio plays an essential role in determining the timing of mitosis and cell division. Recently, 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 long range goal of this research is to develop mathematical models of the cell division cycle in order to build secure, reliable connections between hard-won molecular details of the control mechanisms and classical observations of the behavior of the intact regulatory system. The model will describe the regulation of MPF activity by phosphorylation, and how the phosphorylation state of MPF is determined by the DNA-to-protein ratio of the cell. The mathematical approach is a tool to refine our assumptions and guide our reasoning about the essential events of cell growth and division. %%% The goal of this research is to develop mathematical models of the cell division cycle. The mathematical modeling will be based on recent experimental evidence concerning the biochemical control mechanisms involved in this fundamental life process. The mathematical models will be useful in further refining the interpretations of experimental data and as a guide in planning future experiments that ultimately should lead to a thorough understanding of how the cell division cycle is regulated.

细胞分裂周期是某些细胞周期性的重复。 事件-DNA合成，有丝分裂和胞质分裂-将一个 单个细胞分裂成两个子细胞。 细胞分裂必须 与整体细胞生长协调;否则，细胞可能会变得 任意大或极小。 通过观察细胞 对分裂周期的扰动做出反应，细胞生物学家 发现DNA与蛋白质的比例在 决定有丝分裂和细胞分裂的时间。 最近， 分子研究揭示了四类蛋白质， 突出参与分工控制机制。 两 蛋白质（cdc 2和细胞周期蛋白）联合收割机形成异二聚体（“有丝分裂 促进因子，”或MPF），当激活时，触发所有的 有丝分裂和细胞分裂的主要事件。 强积金的活动是， 依次由蛋白激酶和蛋白磷酸酶控制 决定MPF的磷酸化状态。 远程 本研究的目标是建立细胞的数学模型 以建立安全、可靠的连接 控制机制的来之不易的分子细节， 经典的观察行为的完整的调节 系统 该模型将描述强积金活动的监管， 磷酸化，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。 的 数学方法是一种工具，可以完善我们的假设， 我们对细胞生长的基本事件的推理， 师. %%% 本研究的目标是建立数学模型， 细胞分裂周期 数学建模将基于 关于生化控制的最新实验证据 这一基本生命过程中的机制。 的 数学模型将有助于进一步完善 实验数据的解释，并作为规划的指导 未来的实验，最终应该导致一个彻底的 了解细胞分裂周期是如何调节的。