CAREER: Site-Directed Spin Labeling EPR Applications in Intrinsically Unstructured Proteins

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The research project aims to utilize an electron paramagnetic resonance (EPR) based methodology to study the structure and conformation of a class of proteins that are termed natively unstructured, meaning they have no stable three dimensional structures. Nearly one third of proteins are predicted to function as unstructured motifs, and very few biophysical methods can be utilized to investigate this class of proteins. Through this research, the EPR based methods will be developed, and two classes of proteins will be investigated. The first is a peptide-based inhibitor of an aspartic protease. Results from these studies can be important for understanding how natural peptides are utilized as enzymatic inhibitors, thus potentially providing information about the rational design of new classes of chemicals or peptide-based inhibitors. The second protein is involved in regulating many cellular pathways. Results from this study will provide insights on how proteins can regulate multiple pathways without adopting a well defined structural motif.The participation of undergraduate students (particularly women and those from underrepresented groups) in research in biological magnetic resonance, which spans the fields of biology, chemistry and physics, serves as the central theme of this CAREER project that links research and educational objectives. Specifically, this integration is obtained by a three-tiered approach. One aspect is the recruiting of students into the research laboratory from undergraduate biochemistry and biophysical chemistry labs, where students can directly apply the theory and experimental skills learned in the classroom to a real research setting. The second aspect is the targeting undergraduate students within their first year of college. At The University of Florida (UF), a variety of programs are already in place that provide pools of students for this purpose: underrepresented minorities from the University Minorities Mentoring Program (UMMP), UF undergraduate students (Beckman Scholars, HHMI, REU), and high-school students from the Student Science Training Program (SSTP), organized by UF's Center for Pre-collegiate Education and Training (CPET). The third tier is the development of a summer research exchange program, with other EPR groups within the Southeastern USA, that aims to provide cross-discipline training for undergraduates in both physics and biology as related to EPR spectroscopy. This project is receiving co-funding from the Experimental Physical Chemistry Program of the Chemistry Division.