Investigation of the yeast prion [SWI+]

酵母朊病毒的研究 [SWI]

• 批准号: 1122135
• 负责人: Liming Li
• 金额: $ 78.16万
• 依托单位: Northwestern University at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-11-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1122135&HistoricalAwards=false
• 关键词: Investigation; yeast; prion; SWI+

Intellectual Merit: There are a group of atypical genetic elements in the budding yeast, S. cerevisiae that are known as "yeast prions" because they are transmitted as altered, stable conformations of proteins. This is similar to infectious agents that have been characterized in mammalian systems. Yeast prion studies have provided valuable information on protein folding, information about proteins that assist folding of other macromolecules (molecular chaperone function), and information about protein-based infectivity. This project examines the molecular mechanisms responsible for the prion conformational switch of Swi1p. This protein functions as a subunit of an evolutionarily conserved complex named SWI/SNF, whose function is to remodel chromatin, the fundamental unit of DNA and histone proteins that condenses to form chromosomes. As condensed chromatin represses gene expression, chromatin remodeling by SWI/SNF plays an important role in regulation of gene expression. A combined approach of biochemistry, genetics, and cell biology will be used to 1) examine the structural requirement of Swi1p for prion formation and transmission; 2) identify interaction partners and cellular factors essential for Swi1 prion propagation; and 3) elucidate the biological significance of the Swi1 prion. Results from this investigation will significantly add to the understanding of prion biology and the role of Swi1 prion in chromatin-remodeling and regulation of gene expression. Broader Impact: In addition to the intellectual merit, this project will be a platform for training postdoctoral fellows and graduate students as future independent scientists. Summer undergraduate interns will also be recruited from universities/colleges in the Midwest area. Another major educational goal of this project is to establish a High School Science Club program to connect high school students who are underrepresented minorities in the Chicago area with the biological science community in the Feinberg School of Medicine, Northwestern University. This includes after-school programs and summer camps. Planned activities include science-based discussions, talks and demonstrations, and hands-on activities. This project will likely propel the disadvantaged youth in the Chicago area towards further science education and potentially to a science-oriented career.

智力优势：在萌芽中的酵母中有一组非典型的遗传因素，它们被称为“酵母蛋白”，因为它们以改变的、稳定的蛋白质构象传播。这类似于哺乳动物系统中的感染性病原体。酵母蛋白的研究提供了关于蛋白质折叠的有价值的信息，关于帮助其他大分子折叠的蛋白质的信息(分子伴侣功能)，以及关于基于蛋白质的感染性的信息。这个项目研究了Swi1p蛋白的Pron构象开关的分子机制。这种蛋白质的功能是进化上保守的复合体SWI/SNF的一个亚单位，其功能是重塑染色质，染色质是DNA和组蛋白的基本单位，浓缩形成染色体。由于浓缩的染色质抑制基因表达，SWI/SNF的染色质重塑在基因表达调控中起着重要作用。生物化学、遗传学和细胞生物学相结合的方法将被用来1)研究Swi1p对Pron形成和传递的结构要求；2)确定Swi1 Prion繁殖所必需的相互作用伙伴和细胞因子；以及3)阐明Swi1 Prion的生物学意义。这项研究的结果将极大地增加对Pron生物学的了解，以及Swi1 Pron在染色质重塑和基因表达调控中的作用。更广泛的影响：除了学术价值，该项目还将成为培养博士后研究员和研究生成为未来独立科学家的平台。暑期本科实习生也将从中西部地区的大学/学院招聘。该项目的另一个主要教育目标是建立一个高中科学俱乐部计划，将芝加哥地区代表不足的少数族裔的高中生与西北大学范伯格医学院的生物科学社区联系起来。这包括课后计划和夏令营。计划的活动包括以科学为基础的讨论、讲座和演示，以及动手活动。该项目可能会推动芝加哥地区的弱势青年接受进一步的科学教育，并有可能从事以科学为导向的职业。