CAREER: Structure-Function Studies of a Neurotrophin Receptor Isoform with Novel Neural Differentiation Function

Montana State University, Bozeman MT

Investigators

Abstract

Copie 9984562 This research program focuses on solving the three-dimensional structure of the intracellular domain of a naturally occurring neurotrophin receptor isoform, ICD-TK- trkC, which was recently shown, together with P75 receptor activation, to be effective at promoting neuronal differentiation. Modern multi-dimensional (1H, 15N, 13C) NMR methods will be used to determine its 3D structure in solution at high resolution. The goal of this work is to provide structural and molecular data that, together with site-directed mutagenesis experiments and biochemical assays, will bring insight as to the mechanism(s) by which TK- trkC promotes differentiation of neural cells. The objective of this research is to provide fundamental knowledge about key biochemical interactions regulating neuronal development. This research will integrate the PI's major educational initiatives, including the recruitment of Native American students into the sciences, establishment of "hands on" experiences and "mini-rotations" in research laboratories for undergraduate students, and the organization of seminar series and mentorship programs to encourage under-represented student groups to pursue majors and/or research project in science. This project is an integral component of the PI's involvement with the cross-disciplinary research and educational initiatives being developed at Montana State University through an NSF-sponsored (IGERT) graduate training program.