Investigation of the yeast prion [SWI+]

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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.