京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第21474号 / 生博第405号 / 新制||生||53(附属図書館) / 京都大学大学院生命科学研究科高次生命科学専攻 / (主査)教授 松田 道行, 教授 影山 龍一郎, 教授 渡邊 直樹 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

<p>Cellular dynamics arise from intricate interactions among diverse components, such as metabolites, RNAs, and proteins. An in-depth understanding of these interactions requires an integrated approach to the investigation of biological systems. This task can benefit from a combination of mathematical modeling and experimental validations, which is becoming increasingly indispensable for basic and applied biological research. </p> <p>Utilizing a combination of modeling and experimentation, we investigate mammalian cell cycle entry. We begin our investigation by making predictions with a mathematical model, which is constructed based on the current knowledge of biology. To test these predictions, we develop experimental platforms for validations, which in turn can be used to further refine the model. Such iteration of model predictions and experimental validations has allowed us to gain an in-depth understanding of the cell cycle entry dynamics. </p> <p>In this dissertation, we have focused on the Myc-Rb-E2F signaling pathway and its associated pathways, dysregulation of which is associated with virtually all cancers. Our analyses of these signaling pathways provide insights into three questions in biology: 1) regulation of the restriction point (R-point) in cell cycle entry, 2) regulation of the temporal dynamics in cell cycle entry, and 3) post-translational regulation of Myc by its upstream signaling pathways. The well-studied pathways can serve as a foundation for perturbations and tight control of cell cycle entry dynamics, which may be useful in developing cancer therapeutics. </p> <p>We conclude by demonstrating how a combination of mathematical modeling and experimental validations provide mechanistic insights into the regulatory networks in cell cycle entry.</p> / Dissertation