Evolution of silencing proteins in yeast

酵母中沉默蛋白的进化

• 批准号: 1306862
• 负责人: Laura Rusche
• 金额: $ 65.8万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1306862&HistoricalAwards=false
• 关键词: Evolution; silencing; proteins; yeast

Intellectual Merit The advent of new DNA sequencing technologies and a wealth of sequenced genomes have intensified the need to develop innovative approaches for extracting functional insights from these data. Although homology is a useful principle, homologous proteins sometimes have different functions across species, and these differences can reconfigure regulatory pathways governing how organisms respond to environmental changes. Consequently, extrapolating function from model species can be misleading. To understand how proteins acquire new functions and the biological consequences of these changes, this project focuses on a group of proteins named Sir2 deacetylases, which are found in all kingdoms of life. These enzymes are proposed to coordinate life-cycle transitions with nutrient availability. Importantly, Sir2 deacetylases display varied modes of action and may enable species-specific responses to nutritional conditions. This project employs a combination of genome-scale and classical functional studies to investigate the evolutionary history of Sir2 in genetically tractable yeast species. The first part of the project examines how Sir2 orthologs have evolved new functions by acquiring interactions with a variety of protein complexes that repress gene expression, and the second part explores the consequences of such changes as they relate to the physiology of cells. To elucidate the steps by which Sir2 acquired its function in Saccharomyces cerevisiae, the functions of Sir2 orthologs will be compared in species at appropriate evolutionary distances from S. cerevisiae, namely in Candida lusitaniae, a representative species of the Candida clade, and in the yeast Kluyveromyces lactis. As these species have different responses to nutrient levels in terms of specific aspects of their physiology, this project has the potential to elucidate the roles of Sir2 in such responses.Broader Impact This project will provide training opportunities for two graduate students, several Duke undergraduate students conducting independent studies, and summer students participating in two programs designed to encourage disadvantaged students to pursue careers in science. The Duke Summer Research Opportunity Program (SROP) targets undergraduates, and the North Carolina Section Project SEED program supports high school students. In addition, this project will promote the recruitment and retention of female scientists by supporting the careers of a graduate student and the principal investigator, who are both women. Finally, the development of additional yeast species, such as K. lactis and C. lusitaniae, as model organisms will greatly facilitate future studies in molecular evolution by enabling researchers to test their hypotheses using multiple experimentally tractable yeast species that are separated by hundreds of millions of years of evolution.

新的DNA测序技术和大量测序基因组的出现，加剧了开发创新方法从这些数据中提取功能见解的需求。虽然同源性是一个有用的原则，但同源蛋白质有时在不同物种之间具有不同的功能，这些差异可以重新配置生物体如何应对环境变化的调控途径。因此，从模式物种推断功能可能会产生误导。为了了解蛋白质如何获得新的功能以及这些变化的生物学后果，该项目专注于一组名为Sir2脱乙酰酶的蛋白质，它们存在于所有生命王国中。这些酶被建议协调生命周期的过渡与养分的可用性。重要的是，Sir2脱乙酰基酶显示不同的作用模式，并可能使物种特异性反应的营养条件。该项目采用基因组规模和经典功能研究相结合的方式来研究Sir2在遗传上易处理的酵母物种中的进化历史。该项目的第一部分研究了Sir2直系同源物如何通过与抑制基因表达的各种蛋白质复合物的相互作用而进化出新的功能，第二部分探索了这些变化与细胞生理学相关的后果。为了阐明Sir2在酿酒酵母中获得其功能的步骤，将在与S.在酿酒酵母中，即在葡萄牙假丝酵母（Candida lusitaniae）（假丝酵母进化枝的代表性物种）中，以及在乳酸克鲁维酵母（Kluyveromyces lactis）中。由于这些物种在生理学的特定方面对营养水平有不同的反应，本项目有可能阐明Sir 2在这种反应中的作用。更广泛的影响本项目将为两名研究生，几名进行独立研究的杜克大学本科生，和暑期学生参加两个旨在鼓励弱势学生从事科学事业的项目。杜克暑期研究机会计划（SROP）针对本科生，北卡罗来纳州部分项目种子计划支持高中生。此外，该项目还将通过支持一名研究生和一名主要研究员（均为女性）的职业生涯，促进招聘和留住女科学家。最后，开发其他酵母菌种，如K。lactis和C. lusitaniae作为模式生物将极大地促进未来的分子进化研究，使研究人员能够使用多个实验上易于处理的酵母物种来测试他们的假设，这些酵母物种被数亿年的进化所分开。