Role of Mediator in Heat Shock Gene Regulation

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Intellectual Merit. Genes are linearly arrayed on chromosomes, and their basic features are preserved between simple and complex organisms. This research uses a model organism, baker's yeast (Saccharomyces cerevisiae), to explore the ways in which genes are regulated. In both yeast and humans, genes are either turned on (activated) or off (repressed) as a consequence of the activities of specific proteins that bind DNA in a sequence-specific (gene-specific) fashion. This research will focus on studying the detailed role of a large, evolutionarily conserved protein complex termed Mediator that receives signals from these DNA-binding proteins and integrates them in a way that dictates the expression of individual genes. Thus, Mediator function is akin to that of a computer: it processes large amounts of input information, in the form of intracellular signals, and creates an output, e.g., the complex pattern of gene expression that defines the unique biology of an organism or cell type. This research will take advantage of a set of unique genetic mutations within five subunits centered at Mediator's core. These mutations strongly perturb the expression of genes that respond to environmental stresses such as elevated temperature, chemical toxicity, or oxidative stress. Therefore, characterization of the mutations, and the five subunits they affect, will provide important insight into the biological function of Mediator.Broader Impacts. Benefits of this project, beyond the anticipated scientific discoveries, include the training of three full-time Ph.D. graduate students, three high school teachers (who will do summer research internships of six weeks each) and one high school student. The high school student will engage in an intensive 12-month research experience as a participant in LSU Health Science Center's Science and Medicine Academic Research Training program.