Folding and Aggregation of Polyglutamine Peptides and Proteins

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).0852278Murphy Intellectual merit Experimental and theoretical studies of protein aggregation lag considerably behind protein folding studies, because of their much greater complexity. Several researchers have developed molecular dynamics simulations of protein misfolding and aggregation, but the predictions from these simulations have not been experimentally tested. In this project, 'length libraries' of polyglutamine (polyQ) peptides and proteins will be synthesized and characterized for their conformational properties and aggregation propensities.Broader impacts Aggregation of peptides and proteins pose significant challenges in both biotechnology and biomedicine. For example, over 4.5 million Americans suffer from aggregation-linked neurodegenerative diseases. As another example, aggregates in therapeutic recombinant protein preparations reduce pharmacological efficiency, and can threaten patients' health by causing serious immunological responses. Deciphering the causes of aggregation is the first step towards developing rational strategies for controlling aggregation. Graduate students on this project are broadly educated in modern experimental and computational approaches in protein and peptide folding and misfolding, and prepared to take leading roles in academia or in the biotechnology industry. Through active participation in a summer research program, underrepresented minority undergraduates will gain valuable experience and enjoy a sense of accomplishment that will contribute to their continued enthusiasm for research careers.