Coordination of Cell Growth with Cell Division

描述（由申请人提供）：细胞如何决定何时分裂， 这对于理解几乎所有的生物过程至关重要， 扩散是显而易见的。细胞监测其质量的增加， 启动细胞分裂。协调细胞生长与分裂的机制 决定细胞分裂开始的时间，因此，它们是速率 限制了整体细胞增殖。然而，这些机制在很大程度上 未知细胞生长与细胞分裂的不适当协调导致 在许多疾病中，包括所有类型的恶性肿瘤和异常组织 成长与修复该提案旨在确定分子过程， 细胞将它们的生长与细胞分裂相结合，在遗传上易于控制， 简单真核生物酿酒酵母（酵母）。拟议的研究建立 我们已经开发出的鉴定基因产物的方法， 改变细胞生长与细胞分裂的正常耦合。最小化 由于分析的偏差，这些方法完全依赖于细胞何时启动 细胞分裂遗传改变，如基因扩增和 破坏，这可以加速细胞分裂的启动，将是 具体分析。这项建议还试图确定如何不同 营养素影响细胞周期进程并阐明GI细胞周期蛋白的作用 蛋白质在这个过程中GI细胞周期蛋白是已知的起始调节因子 但是受影响的分子途径和确切的 每种细胞周期蛋白的作用尚不清楚。为了实现这些目标， 拟议的研究依赖于明确的连续细胞培养，以精确地 将细胞周期进程与特定代谢参数相关联。的 细胞分裂的整体调节在酵母和 人类因此，拟议研究的结果将直接影响 细胞生长与分裂的耦合在人类细胞中被感知， 这一过程会导致人类疾病。

DESCRIPTION (PROVIDED BY APPLICANT): How cells determine when to divide is critical for understanding virtually every biological process that cell proliferation is manifest. Cells monitor their increase in mass before they initiate cell division. Mechanisms that coordinate cell growth with division determine the timing of initiation of cell division and, thus, they are rate limiting for overall cell proliferation. Yet, these mechanisms remain largely unknown. Inappropriate coordination of cell growth with cell division results in numerous diseases, including malignancies of all types and abnormal tissue growth and repair. This proposal seeks to identify molecular processes by which cells couple their growth with cell division, in the genetically tractable simple eukaryote Saccharomyces cerevisiae (yeast). The proposed research builds on methods we have developed for the identification of gene products that can alter the normal coupling of cell growth with cell division. To minimize the bias of the analysis, these methods rely exclusively on when cells initiate cell division. Genetic alterations, such as gene amplifications and disruptions, which can accelerate initiation of cell division, will be specifically analyzed. This proposal also seeks to determine how different nutrients affect cell cycle progression and clarify the role(s) of GI cyclin proteins in this process. GI cyclin proteins are known regulators of initiation of cell division, but the molecular pathways affected and the exact contributions that each cyclin makes are unclear. To reach these goals, the proposed study relies on well-defined continuous cell cultures, to precisely correlate cell cycle progression with specific metabolic parameters. The overall regulation of cell division is highly conserved between yeast and humans. Thus, findings from the proposed study will directly impact on the way that coupling of cell growth with division is perceived in human cells and how this process contributes to human disease.