Yeast Lifespan Chemical Screening (RMI)

酵母寿命化学筛选 (RMI)

• 批准号: 7058477
• 负责人: DAVID S GOLDFARB
• 金额: $ 0.47万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2006-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058477
• 关键词: Saccharomyces cerevisiae; aging; bioassay; chemical registry /resource; drug screening /evaluation; fungal genetics; high throughput technology; life cycle; longevity; phenotype; small molecule

DESCRIPTION (provided by applicant): The goal of this proposal is to exploit a novel high throughput assay capable of screening hundreds of thousands of compounds for affects 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. Preliminary studies screening a library of ~2500 compounds indicates that the DEAD assay can be performed in 384 well plates without constant shaking. When the starting DEAD cell culture is prepared and handled properly, the optical density read-out is readily controlled and highly reproducible. The aim of this proposal is to facilitate DEAD assay screening of chemical libraries in the NIH Small Molecule Repository at Molecular Libraries Screening Centers. Promising compounds can be readily assessed using other lifespan assays in yeast, worms, and fruit flies. The assay results can be easily formatted in raw and processed formats to maximize their sharing and utility to others.

描述（由申请人提供）：该提案的目的是利用一种能够筛选数十万种化合物的新型高通量测定法，以使酿酒酵母中的复制寿命影响。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。初步研究筛选了一个〜2500种化合物的库表明，可以在384个井板中执行死亡测定法，而不会不断摇动。当制备和正确处理起始的死细胞培养物时，光密度读出很容易控制且高度可重现。该提案的目的是促进分子库筛选中心的NIH小分子存储库中化学文库的死测定筛选。可以使用酵母，蠕虫和水果果蝇中的其他寿命测定法评估有希望的化合物。可以轻松地以原始和处理的格式对测定结果进行格式，以最大程度地提高其与他人的共享和实用性。