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

项目摘要/摘要 这项要求行政补充以促进职业重新进入的请求将允许Jill B.Jensen博士继续 在莎罗娜·戈登博士的指导下，作为一名研究助理教授，走向独立的道路。她 将在母公司R35赠款范围内从事TRPM2项目，从事职业发展，并制定 一个独立的研究项目。该项目研究了调控钙离子和腺苷二磷酸的分子机制。 TRPM2通道中核糖驱动的构象重排。詹森博士将在戈登博士的指导下进行培训 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；以及膜片钳荧光法。 她将在斯蒂芬·史密斯博士的实验室学习定量多重免疫沉淀。努力做到这一点 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，以扩大她的科学影响范围。 在戈登博士、华德曼博士和拉米雷斯博士的积极指导下， 在发展活动方面，詹森博士还将发展一条独立的科学探究路线，扩大她 职业关系网，提高全国知名度，培训为导师，并申请自己的研究资助，如 研究计划中所描述的。

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.