Investigation of the yeast prion [SWI+]

智力优势：在出芽酵母（酿酒酵母）中有一组非典型遗传元素，被称为“酵母朊病毒”，因为它们以改变的、稳定的蛋白质构象传播。这与哺乳动物系统中的传染性病原体相似。酵母朊病毒的研究提供了关于蛋白质折叠的宝贵信息，关于蛋白质协助其他大分子折叠的信息（分子伴侣功能），以及关于蛋白质传染性的信息。本项目研究Swi1p的朊病毒构象开关的分子机制。该蛋白作为进化保守复合物SWI/SNF的一个亚基，其功能是重塑染色质，染色质是DNA和组蛋白凝聚形成染色体的基本单位。由于浓缩染色质抑制基因表达，SWI/SNF对染色质的重塑在基因表达调控中起着重要作用。将使用生物化学、遗传学和细胞生物学相结合的方法来1)检查Swi1p对朊病毒形成和传播的结构要求；2)确定Swi1朊病毒传播所需的相互作用伙伴和细胞因子；3)阐明Swi1朊病毒的生物学意义。本研究结果将有助于进一步了解朊病毒生物学以及Swi1朊病毒在染色质重塑和基因表达调控中的作用。更广泛的影响：除了智力价值，该项目将成为培养博士后和研究生成为未来独立科学家的平台。夏季本科生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项目，将芝加哥地区未被充分代表的少数民族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。这包括课外活动和夏令营。计划的活动包括基于科学的讨论、讲座和演示以及实践活动。这个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。

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.