Computational Models of Cell Growth and Division

细胞分裂周期是一系列事件，一个活细胞复制其所有成分，并将它们分裂到两个子细胞之间，以便每个子细胞拥有重复这一过程所需的信息和机制。由于细胞周期是所有生物生长、发育和繁殖的基础，细胞周期受到分子生物学家的密切研究，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，调控机制是高度保守的，同源成分跨物种屏障发挥作用，从酵母到青蛙再到人类。这个控制系统的许多细节现已为人所知，直观的方法无法解释这些分子组成之间的复杂相互作用。迫切需要新的知识获取和发展方法。为此，首席研究员创建了计算工具来对细胞周期控制系统进行建模，分析其属性，并将假设的机制与细胞分裂的实际行为进行比较。这个项目是通过在新的方向上追求以前的计算方法来扩展对细胞周期控制的理解。首席研究员团队将在芽酵母和分裂酵母中构建全面的生长和分裂模型，重点研究启动DNA合成、退出有丝分裂和选择新的生长区的分子机制。他们还将构建新的减数分裂细胞分裂(有性繁殖必不可少)和胚胎发育过程中细胞周期调整的模型。从对酵母和胚胎的控制系统建模中学到的东西，随后将被转移到调控哺乳动物细胞生长和分裂的更为复杂的生化反应网络中。除了开发分析遗传调控机制的新方法和在新兴的计算分子生物学领域培训年轻人外，该项目还有望对调控细胞生长和分裂的分子机制产生新的理论见解。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(例如，寄生虫控制、神经细胞再生和癌症治疗)的实际发展中。

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).