Computational Models of Cell Growth and Division

点击翻译按钮获取中文摘要

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).