Computational Models of Cell Growth and Division

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。迫切需要新的知识获取和发展方法。出于这个原因，首席研究员已经创建了计算工具来模拟细胞周期控制系统，分析其特性，并将假设的机制与分裂细胞的实际行为进行比较。本计画将借由在新的方向上追求先前的计算方法来扩展对细胞周期控制的了解。主要研究者的团队将构建芽殖酵母和裂殖酵母生长和分裂的综合模型，重点研究DNA合成起始、有丝分裂退出和新生长区选择的分子机制。他们还将构建减数分裂细胞分裂（有性生殖所必需的）和胚胎发生过程中细胞周期修饰的新模型。从酵母和胚胎控制系统的建模中所学到的东西将被转移到哺乳动物细胞中更复杂的生物化学反应网络中，调节生长和分裂。除了开发新的方法来分析遗传调控机制和培训年轻人在新兴的计算分子生物学领域，该项目有望产生新的理论见解调节细胞生长和分裂的分子机制。对细胞周期控制的更深入理解最终将被用于农业、组织工程和医学的实际发展（例如，寄生虫控制、神经细胞再生和癌症治疗）。

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 methods of knowledge acquisition and development are desperately needed. For this reason, the Principal Investigator has created computational tools to model the cell-cycle control system, analyze its properties, and compare hypothetical mechanisms to the actual behavior of dividing cells. This project is to extend the understanding of cell cycle control by pursuing previous computational approach in new directions. The Principal Investigator's team will construct comprehensive models of growth and division in budding yeast and fission yeast, focusing on the molecular mechanisms that underlie initiation of DNA synthesis, exit from mitosis, and selection of new growth zones. They will also construct new models of meiotic cell division (essential to sexual reproduction) and cell-cycle modifications during embryogenesis. What is learned from modeling the control systems in yeasts and embryos will then be transferred to the vastly more complicated network of biochemical reactions regulating growth and division in mammalian cells. Aside from developing new approaches to the analysis of genetic regulatory mechanisms and training young people in the burgeoning field of computational molecular biology, this project promises to yield novel theoretical insights into the molecular machinery regulating cell growth and division. Deeper understanding of cell-cycle control will eventually be parlayed into practical developments in agriculture, tissue engineering, and medicine (e.g., parasite control, nerve cell regeneration, and cancer treatment).