GENETIC AND MOLECULAR ANALYSIS OF AGING AND APOPTOSIS IN THE YEAST, SACCHAROMYCE

酵母、酵母菌衰老和细胞凋亡的遗传和分子分析

• 批准号: 7381364
• 负责人: NICANOR AUSTRIACO
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381364
• 关键词: GENETIC; MOLECULAR; ANALYSIS; AGING; APOPTOSIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cellular aging and apoptosis are two processes that have been implicated in human disease. For instance, it is now clear that both are potent anti-cancer mechanisms. Cells that either escape senescence or bypass apoptosis in response to oncogenic stimuli can undergo malignant transformation. The ability of cells to evade programmed cell death has been called a "hallmark of cancer". Significantly, there is good evidence that disabling mutations senescence and apoptosis contribute to the anti-tumor activity of many chemotherapeutic drugs and that apoptosis can result in multi-drug resistance. The budding yeast Saccharomyces cerevisiae has served as a useful model for complex physiological processes of metazoan cells, including aging and apoptotic cell death. Molecular mechanisms of both these processes appear to be conserved and genetic determinants have been identified in yeast with orthologues in higher organisms. This research program outlines several genetic strategies to identify molecular links between these two processes in yeast. It will exploit the primary advantage of the yeast system over its mammalian counterpart as a model system for aging because yeast cells represent aging-related processes typical of higher organisms but age more quickly. Yeast cells are easier to work with because they age and reach senescence within a matter of weeks. Mammalian cells, on the other hand, take months to undergo senescence, while mammalian organisms take years, if not decades, to age. Given the remarkable conservation of the aging and apoptotic pathways across diverse species, this analysis, which takes advantage of the genetic tools and ease of study associated with the yeast system, should lead to further insights into the analogous processes in higher organisms including human beings.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。细胞衰老和细胞凋亡是与人类疾病有关的两个过程。例如，现在很明显，两者都是有效的抗癌机制。响应致癌刺激而逃避衰老或绕过凋亡的细胞可能会发生恶性转化。细胞逃避程序性细胞死亡的能力被称为“癌症的标志”。值得注意的是，有充分的证据表明，失能突变衰老和细胞凋亡有助于许多化疗药物的抗肿瘤活性，并且细胞凋亡可导致多药耐药性。芽殖酵母酿酒酵母已成为后生动物细胞复杂生理过程（包括衰老和细胞凋亡）的有用模型。这两个过程的分子机制似乎都是保守的，并且已经在酵母中鉴定出遗传决定因素与高等生物中的直系同源物。该研究计划概述了几种遗传策略，以识别酵母中这两个过程之间的分子联系。它将利用酵母系统相对于哺乳动物系统的主要优势作为衰老模型系统，因为酵母细胞代表了高等生物体典型的衰老相关过程，但衰老得更快。酵母细胞更容易使用，因为它们会在几周内老化并达到衰老状态。另一方面，哺乳动物细胞需要数月的时间才能衰老，而哺乳动物生物体则需要数年甚至数十年的时间才能衰老。鉴于不同物种之间衰老和凋亡途径的显着保守性，这项分析利用了与酵母系统相关的遗传工具和易于研究的优势，应该可以进一步深入了解包括人类在内的高等生物体中的类似过程。