Molecular Screen for Lifespan Extension in Yeast (RMI)

延长酵母寿命的分子筛选 (RMI)

• 批准号: 6879887
• 负责人: DAVID S GOLDFARB
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2005-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879887
• 关键词: Saccharomyces cerevisiae; chemical structure function; computer program /software; computer system design /evaluation; computer system hardware; drug design /synthesis /production; drug screening /evaluation; fungal genetics; gene expression; genetic promoter element; high throughput technology; method development; microorganism growth; technology /technique development

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and test a novel high throughput assay capable of screening hundreds of thousands of compounds for effects on replicative lifespan in the yeast Saccharomyces cerevisiae. Key aspects of aging are conserved between yeast and humans, including signaling, regulatory, and effector pathways. Yeast has been a valuable model system for the discovery and elucidation of conserved aging genes such as SIR2 and their modes of regulation, but only the surface of the field has been scratched. The screening of chemical libraries with this assay should result in the identification of compounds that affect the activities of known and as yet undiscovered cellular targets with roles in aging and lifespan. The "death of daughters" (DEAD) replicative lifespan assay provides cell-based phenotypic screen that will allow us to address an entirely new order of questions about the molecular mechanism and control of aging and lifespan. This high throughput assay will allow us to investigate the genomics of lifespan, screen chemical libraries for compounds that affect lifespan, and study the genetics of lifespan among natural populations. The specific aims of this proposal are directed at developing optimized genetic platforms and automated high throughput assay formats with simple readouts for replicative lifespan. The long term goal of this project is to saturate the function yeast genome (the proteome) with compounds that affect lifespan, many of which should find applications to both basic and applied studies. Since approximately one out of five yeast genes has a human homolog, we believe it likely that some of these targets, and their roles in aging or age-related diseases, will be conserved in humans. Thus, yeast remains fertile ground for gene discovery, for the elucidation of conserved aging mechanisms, and for studies of functional senescence.

描述（由申请人提供）：该提案的目的是开发和测试一种能够筛选成千上万种化合物的新型高通量测定法，以对酿酒酵母的酵母糖疗法中的复制寿命产生影响。 衰老的关键方面是酵母和人之间的保守，包括信号，调节和效应途径。 酵母是一种有价值的模型系统，用于发现和阐明保守衰老基因（例如Sir2及其调节模式），但仅抓取了田间的表面。 使用该测定法对化学文库进行筛选应导致鉴定出影响已知和尚未发现的细胞靶标的化合物，并在衰老和寿命中作用。 “女儿的死亡”（死）复制寿命测定提供了基于细胞的表型筛选，这将使我们能够解决有关分子机制和衰老和寿命的全新问题。 这种高吞吐量测定将使我们能够研究影响寿命的化合物的寿命，筛选化学文库的基因组学，并研究自然种群中寿命的遗传学。 该提案的具体目的旨在开发优化的遗传平台和自动化的高通量测定格式，并具有简单的复制寿命读数。 该项目的长期目标是用影响寿命的化合物使功能酵母基因组（蛋白质组）饱和，其中许多都应在基础研究和应用研究中找到应用。 由于五个酵母基因中大约有一个具有人类同源物，因此我们认为，其中一些靶标及其在衰老或与年龄有关的疾病中的作用可能在人类中得到保存。 因此，酵母仍然是基因发现，阐明保守衰老机制以及功能衰老研究的肥沃基础。