Conformational Energetics and Heterogeneity to Reveal Gating Mechanisms of TRPV and TRPM Ion Channels

University Of Washington, Seattle WA

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Abstract

Project Summary/Abstract This request for an administrative supplement to facilitate career re-entry will allow Dr. Jill B. Jensen to pursue a path to independence as a Research Assistant Professor under the mentorship of Dr. Sharona Gordon. She will work on the TRPM2 project in the scope of the parent R35 grant, engage in career development, and develop an independent research program. This project addresses the molecular mechanisms governing Ca2+- and ADP Ribose-driven conformational rearrangements in TRPM2 channels. Dr. Jensen will train under Dr. Gordon to gain expertise in transition metal ion FRET using both steady-state and time-resolved fluorescence measurement; using amber codon suppression to introduce unnatural amino acids; and patch clamp fluorometry. She will learn quantitative multiplex immunoprecipitation in the laboratory of Dr. Stephen Smith. Work on this project will provide Dr. Jensen with tools in biochemistry and molecular biophysics to expand her scientific reach. With active mentoring support from Dr. Gordon, Dr. Wordeman, and Dr. Ramirez and directed career development activities, Dr. Jensen will also develop an independent line of scientific inquiry, expand her professional network, increase national visibility, train as a mentor, and apply for her own research grant, as described in the research plan.