MPS-Ascend: A Proteomic Approach to Understand and Improve Endosomal Escape

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。Daniel Brauer被授予NSF数学和物理科学提升博士后研究奖学金（NSF MPS-Ascend），以开展一项与扩大STEM中代表性不足群体参与相关的研究和活动计划。Brauer博士的研究项目名为“MPS-Ascend：一种了解和改善内体逃逸的蛋白质组学方法”，由一位赞助科学家指导。该奖学金的主办机构是加州大学伯克利分校，赞助科学家是Alanna Schepartz博士。本研究拟利用微型蛋白ZF5.3作为工具，增加对参与内体逃逸的细胞机制的理解，并阐明内体逃逸的结构-活性关系。这项工作将开发一种新的、时间依赖的、基于光催化剂的接近标记策略，以识别ZF5.3通过内吞途径到达细胞质的蛋白质和脂质伴侣。这项工作还将创建一个高通量的内体逃逸定量分析，以建立结构活性关系，指导ZF5.3携带和不携带蛋白质货物的逃逸。这项工作的成功实施可能会使我们对细胞内蛋白疗法有更深入的了解。PI计划使用数据驱动的框架来改善加州大学伯克利分校化学学院的学术氛围，并包容少数族裔。定量调查数据将用于产生有针对性的解决方案，以提高加州大学伯克利分校化学学院博士后学者的包容性和持久性，以便有才华和多样化的候选人晋升为未来的教师领导者。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Daniel Brauer is awarded a NSF Mathematical and Physical Sciences Ascending Postdoctoral Research Fellowship (NSF MPS-Ascend) to conduct a program of research and activities related to broaden participation by groups underrepresented in STEM. This fellowship to Dr. Brauer supports the research project entitled “MPS-Ascend: A Proteomic Approach to Understand and Improve Endosomal Escape", under the mentorship of a sponsoring scientist. The host institution for the fellowship is the University of California Berkeley, and the sponsoring scientist is Dr. Alanna Schepartz. This proposal intends to use the miniature protein ZF5.3 as a tool to increase the understanding of the cellular machinery involved in endosomal escape and to shed light on endosomal escape structure-activity relationships. The proposed work will develop a novel, time dependent, photocatalyst based proximity labeling strategy to identify the protein and lipid partners of ZF5.3 as it traverses the endocytic pathway to reach the cytosol. The work will also create a high throughput, quantitative assay for endosomal escape to establish structure activity relationships that guide the escape of ZF5.3 with and without protein cargo. Successful implementation of this work may allow for greater understanding of intracellular protein therapeutics. The PI intends to use a data driven framework for improving the academic climate and inclusion of minoritized individuals in the UC Berkeley College of Chemistry. Quantitative survey data will be used to generate targeted solutions to improve inclusion and persistence among UC Berkeley College of Chemistry postdoctoral scholars so that talented and diverse candidates advance to roles as future faculty leaders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.