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

该奖项全部或部分根据2021年美国救援计划法案（公法117-2）资助。丹尼尔布劳尔被授予NSF数学和物理科学上升博士后研究奖学金（NSF MPS-Ascend），以开展与扩大STEM中代表性不足的群体参与有关的研究和活动计划。Brauer博士的这项奖学金在赞助科学家的指导下支持题为“MPS-Ascend：了解和改善内体逃逸的蛋白质组学方法”的研究项目。该研究金的主办机构是加州伯克利大学，赞助科学家是Alanna Schepartz博士。 该提案旨在使用微型蛋白ZF 5.3作为工具，以增加对内体逃逸所涉及的细胞机制的理解，并阐明内体逃逸的结构-活性关系。拟议的工作将开发一种新的，时间依赖性的，基于光催化剂的邻近标记策略，以识别ZF 5.3的蛋白质和脂质伴侣，因为它穿过内吞途径到达胞质溶胶。这项工作还将建立一种高通量的内体逃逸定量分析方法，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细胞内蛋白质治疗更好地理解。PI打算使用数据驱动的框架来改善学术氛围，并将少数群体纳入加州大学伯克利分校化学学院。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，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NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响力审查标准进行评估来支持。

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.