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RUI: Scaffold or Assembly Line: How Does Atg11 Organize its Binding Partners for the Initiation of Selective Autophagy?

RUI：支架或装配线：Atg11 如何组织其结合伙伴以启动选择性自噬？

基本信息

批准号：
1613653
负责人：
Steven Backues
金额：
$ 29.74万
依托单位：
Eastern Michigan University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1613653&HistoricalAwards=false
关键词：
RUI Scaffold Assembly Line How

项目摘要

The subject of this research project is selective autophagy, a cellular clean-up and recycling process used by animals, plants and fungi to maintain cellular function. This project will improve America's competitiveness by contributing to the education of a diverse and technically literate workforce. It will create a research-rich learning environment for biochemistry students at Eastern Michigan University, a primarily undergraduate institution that serves a racially and socioeconomically diverse population of students. It will do this by supporting a cutting-edge research program that will directly engage ~10-12 undergraduate and Master's level students in mentored scientific research projects as well as creating semester-long guided research experiences for ~30-36 additional undergraduates as part of a research-based senior-level biochemistry lab. Multiple studies have shown that the most effective way for students to learn science is by participating in authentic scientific research. Therefore, this project will not only advance our fundamental understanding of the natural world but also train the next generation of scientists. Selective autophagy targets damaged or unwanted cellular components, such as toxic protein aggregates or malfunctioning mitochondria, and delivers them to the vacuole/lysosome where they are destroyed and their constituents recycled. This research focuses on understanding the basic mechanisms of selective autophagy in the model organism baker's yeast. One of the key proteins that guides the process of selective autophagy is Atg11, which interacts with a number of other autophagy proteins and organizes them into a functional protein complex. This research will explain how Atg11 organizes this complex by determining the characteristics of Atg11's interactions with its protein partners. Specifically, it will determine whether Atg11can bring together all of its partners at once, in the manner of a scaffold, or whether it interacts with them one at a time, in the manner of an assembly line. This information will help us to understand how selective autophagy actually occurs, not only in yeast but also many other organisms that share a similar machinery, including humans.

本研究项目的主题是选择性自噬，动物，植物和真菌用于维持细胞功能的细胞清理和回收过程。这个项目将通过促进多样化和技术熟练的劳动力的教育来提高美国的竞争力。它将为东密歇根大学（Eastern Michigan University）的生物化学学生创造一个研究丰富的学习环境。东密歇根大学是一所主要的本科院校，为来自不同种族和社会经济背景的学生提供服务。它将通过支持一个前沿研究项目来实现这一目标，该项目将直接吸引约10-12名本科生和硕士生参与指导的科学研究项目，并为约30-36名额外的本科生创造长达一个学期的指导研究经验，作为研究型高级生物化学实验室的一部分。多项研究表明，学生学习科学最有效的方式是参与真实的科学研究。因此，这个项目不仅将促进我们对自然世界的基本认识，而且还将培养下一代科学家。选择性自噬以受损或不需要的细胞成分为目标，如有毒的蛋白质聚集体或故障的线粒体，并将它们递送到液泡/溶酶体，在那里它们被破坏并回收其成分。本研究的重点是了解模式生物面包酵母选择性自噬的基本机制。引导选择性自噬过程的关键蛋白之一是Atg11，它与许多其他自噬蛋白相互作用，并将它们组织成功能性蛋白复合物。这项研究将通过确定Atg11与其蛋白质伙伴相互作用的特征来解释Atg11如何组织这种复合物。具体来说，它将决定atg11是否能够以脚手架的方式将其所有合作伙伴聚集在一起，还是以装配线的方式一次与它们交互。这些信息将帮助我们了解选择性自噬是如何发生的，不仅在酵母中，而且在许多其他具有类似机制的生物中，包括人类。