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

本研究项目的重点是解决自然存在的神经营养因子受体异构体ICD-TK- trkC的细胞内结构域的三维结构，该异构体最近被证明与P75受体激活一起可有效促进神经元分化。现代多维（1H, 15N, 13C）核磁共振方法将在高分辨率下确定其在溶液中的三维结构。这项工作的目标是提供结构和分子数据，连同定点诱变实验和生化分析，将使人们了解TK- trkC促进神经细胞分化的机制。本研究的目的是提供关于调节神经元发育的关键生化相互作用的基础知识。这项研究将整合PI的主要教育倡议，包括招募美国原住民学生进入科学领域，为本科生在研究实验室建立“实践”经验和“迷你轮转”，以及组织系列研讨会和指导计划，以鼓励代表性不足的学生群体追求科学专业和/或研究项目。该项目是PI参与蒙大拿州立大学通过nsf赞助的研究生培训项目（IGERT）开展的跨学科研究和教育活动的一个组成部分。

Copie9984562This 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.