Coordination of Cell Growth with Cell Division

细胞生长与细胞分裂的协调

• 批准号: 6384127
• 负责人: MICHAEL S POLYMENIS
• 金额: $ 24.58万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384127
• 关键词: Saccharomyces cerevisiae; cell cycle; cell growth regulation; cell proliferation; cyclins; cytogenetics; enzyme activity; eukaryote; fungal genetics; genetic regulation; glutamate ammonia ligase; growth media; microorganism culture; natural gene amplification; nitrogen metabolism; tissue /cell culture

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.

描述（由申请人提供）：细胞如何决定何时分裂 对于理解细胞的几乎所有生物过程至关重要 扩散现象很明显。细胞在进入细胞之前会监测其质量的增加 启动细胞分裂。协调细胞生长与分裂的机制 确定细胞分裂开始的时间，因此，它们是速率 限制整体细胞增殖。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 许多疾病，包括所有类型的恶性肿瘤和异常组织 生长和修复。该提案旨在确定分子过程 细胞将其生长与细胞分裂结合起来，以遗传易处理的方式 简单真核生物酿酒酵母（酵母）。拟议的研究构建 我们开发的用于鉴定基因产物的方法可以 改变细胞生长与细胞分裂的正常耦合。为了尽量减少 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，例如基因扩增和 破坏，可以加速细胞分裂的开始， 具体分析了。该提案还试图确定如何不同 营养物质影响细胞周期进程并阐明胃肠道细胞周期蛋白的作用 这个过程中的蛋白质。 GI 细胞周期蛋白是已知的起始调节因子 细胞分裂，但受影响的分子途径和确切的 每种细胞周期蛋白的贡献尚不清楚。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。这 细胞分裂的总体调节在酵母和 人类。因此，拟议研究的结果将直接影响 在人类细胞中可以感知到细胞生长与分裂的耦合，以及如何 这个过程会导致人类疾病。