Coordination of Cell Growth with Cell Division

描述(申请人提供)：细胞如何决定何时分裂 对于理解细胞的几乎每一个生物过程至关重要 扩散是显而易见的。细胞监测它们的质量增加在它们 启动细胞分裂。协调细胞生长和分裂的机制 确定细胞分裂开始的时间，因此，它们的速率 限制细胞的整体增殖。然而，这些机制在很大程度上仍然存在 未知。细胞生长与细胞分裂结果的不适当协调 在许多疾病中，包括所有类型的恶性肿瘤和异常组织 成长和修复。这项提议寻求确定分子过程，通过这些过程 细胞将其生长与细胞分裂结合在一起，在遗传上容易控制的 简单的真核生物酿酒酵母(酵母)。拟议的研究建立了 关于我们已经开发的用于鉴定可以 改变细胞生长和细胞分裂的正常耦合。要最小化 分析的偏差，这些方法完全依赖于细胞启动的时间 细胞分裂。基因改变，如基因扩增和 可以加速细胞分裂的破坏将是 具体分析了。这项提案还试图确定不同 营养物质影响细胞周期进程并阐明GI周期蛋白的作用(S) 在这一过程中的蛋白质。GI细胞周期蛋白是已知的启动调节因子 细胞分裂，但影响的分子途径和确切的 目前尚不清楚每个周期蛋白的贡献。为了实现这些目标， 建议的研究依赖于明确定义的连续细胞培养，准确地说 将细胞周期进程与特定的代谢参数相关联。这个 酵母和酵母之间对细胞分裂的总体调控是高度保守的 人类。因此，拟议研究的结果将直接影响 细胞生长和分裂的耦合在人类细胞中被感知到，以及如何 这一过程导致了人类疾病。

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.