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资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。细胞衰老和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。响应致癌刺激而逃脱衰老或旁路凋亡的细胞会发生恶性转化。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，残疾突变衰老和凋亡有助于许多化学治疗药物的抗肿瘤活性，而细胞凋亡可能导致多药耐药性。酿酒酵母的萌芽酵母菌已成为多唑细胞复杂生理过程的有用模型，包括衰老和凋亡细胞死亡。这两个过程的分子机制似乎是保守的，并且在较高生物体的直系同源物中已经鉴定出遗传决定因素。该研究计划概述了几种遗传策略，以确定酵母中这两个过程之间的分子联系。它将利用酵母系统比其哺乳动物对应物的主要优势作为衰老的模型系统，因为酵母细胞代表了典型的较高生物体的衰老相关过程，但更快地衰老。酵母细胞更容易使用，因为它们会在几周内衰老并达到衰老。另一方面，哺乳动物细胞需要几个月的时间才能经历衰老，而哺乳动物的生物会花费数年的时间（即使不是几十年）的年龄。鉴于对各种物种的衰老和凋亡途径的显着保护，这种分析利用了与酵母系统相关的遗传工具和易于研究，应进一步深入了解包括人类在内的较高生物体中的类似过程。