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

职业：具有新型神经分化功能的神经营养蛋白受体亚型的结构功能研究

• 批准号: 9984562
• 负责人: Valerie Copie
• 金额: $ 49.9万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9984562&HistoricalAwards=false
• 关键词: CAREER; Structure; Function; Studies; Neurotrophin

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.

Copie9984562该研究项目的重点是解决天然存在的神经营养蛋白受体亚型 ICD-TK-trkC 细胞内结构域的三维结构，最近显示它与 P75 受体激活一起可有效促进神经元分化。 现代多维（1H、15N、13C）NMR 方法将用于以高分辨率确定其溶液中的 3D 结构。这项工作的目标是提供结构和分子数据，结合定点诱变实验和生化测定，将深入了解 TK-trkC 促进神经细胞分化的机制。这项研究的目的是提供有关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的主要教育举措，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中建立“实践”经验和“迷你轮换”，以及组织研讨会系列和导师计划，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 资助的 (IGERT) 研究生培训计划开发的跨学科研究和教育计划的一个组成部分。