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

项目概要/摘要 这一要求的行政补充，以促进职业生涯的重新进入将允许吉尔博士B。让詹森继续 一条独立的道路，作为一个研究助理教授在博士的指导下。她 将在R35赠款范围内从事TRPM 2项目，从事职业发展，并发展 独立的研究项目。本项目主要研究Ca 2 +-和ADP的分子调控机制 TRPM 2通道中核糖驱动的构象重排。詹森博士将在戈登博士手下受训 获得使用稳态和时间分辨荧光的过渡金属离子FRET的专业知识 测量;使用琥珀密码子抑制引入非天然氨基酸;和膜片钳荧光测定法。 她将在Stephen Smith博士的实验室学习定量多重免疫沉淀。工作就这一 该项目将为詹森博士提供生物化学和分子生物物理学方面的工具，以扩大她的科学范围。 在戈登博士、沃德曼博士和拉米雷斯博士的积极指导支持下， 发展活动，詹森博士还将开发一个独立的科学探究路线，扩大她的 专业网络，提高国家知名度，作为导师进行培训，并申请自己的研究补助金， 在研究计划中描述。

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.