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

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。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中代表性不足群体的参与相关的研究和活动。这笔给布劳尔博士的奖学金支持了一位赞助科学家的指导下的题为“MPS-Ascend：理解和改善内体逃逸的蛋白质组学方法”的研究项目。该奖学金的主办机构是加州大学伯克利分校，赞助科学家是阿兰娜·谢帕茨博士。本提案旨在利用ZF5.3蛋白作为工具，以增加对涉及内体逃逸的细胞机制的了解，并阐明内体逃逸的结构-活性关系。这项拟议的工作将开发一种新的、依赖于时间的、基于光催化剂的邻近标记策略，以确定ZF5.3在穿过内吞途径到达胞浆时的蛋白质和脂肪伙伴。这项工作还将创建一种高通量、定量的内体逃逸分析，以建立结构活性关系，指导ZF5.3在有和没有蛋白质货物的情况下逃逸。这项工作的成功实施可能会使人们更好地理解细胞内蛋白质疗法。国际和平研究所打算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和纳入少数人。定量调查数据将用于生成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，从而使有才华和多样化的候选人晋升为未来的教师领导。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势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.