mRNA decay mechanisms for ER stress recovery

这个项目的目的是建立在我作为一个博士后学者所做的工作，遵循令人兴奋的线索 细胞从压力中恢复的新机制的发现， 我将以独立研究者的身份研究新的领域。我的目标是利用 在UCSF的大量资源和专业知识，这将使我学习新的技术，并扩大我的 研究，并在长期发展我自己的研究计划，重点是mRNA调控及其 与本地化和压力恢复的关系。 作为加州大学旧金山分校乔纳森·韦斯曼实验室的博士后， 细胞通过降解定位于内质网的mRNA来应对折叠应激 在这个隔间里这一途径有许多生理和机制方面， 这是一个尚未探索的领域，可能会提供关于细胞如何在急性应激中存活的见解，一种特定的核酸内切酶如何在细胞中表达， 参与广谱mRNA的衰变，以及定位如何影响mRNA的稳定性， 调控本申请中描述的研究旨在直接解决这些问题， 使用基因组和小规模实验的组合。 这里概述的研究将进一步加深我们对细胞如何生存和适应压力的理解。 ER是一种与多种人类疾病有关的疾病，包括糖尿病和阿尔茨海默氏症 疾病，以及病毒感染。了解细胞如何科普这种情况将有直接的意义 对我们理解这些疾病的机制有很大帮助。例如，肥胖与 已经提出2型糖尿病由ER应激介导，特别是Ire 1，一种蛋白质， 本研究将直接研究功能。

This project is designed to build upon work I have done as a postdoctoral scholar, to follow exciting leads opened up by the discovery of a new mechanism cells employ to recover from stress, and expand these studies into new areas that I will study as an independent investigator. My goals are draw upon the substantial resources and expertise at UCSF that will allow me to learn new techniques and expand my research, and in the longer term to develop my own research program focused on mRNA regulation and its relationship to localization and recovery from stress. As a postdoc in Jonathan Weissman's laboratory at UCSF, I have initially characterized a new pathway by which cells degrade mRNAs localized to the endoplasmic reticulum as a way of coping with folding stress in this compartment. There are many physiological and mechanistic aspects of this pathway that are unexplored and are likely to provide insight into how cells survive acute stress, how a specific endonuclease participates in the decay of a broad spectrum of mRNAs, and how localization affects mRNA stability and regulation. The research described in this application is designed to address each of these issues directly, using a combination of genomic and smaller scale experiments. The research outlined here will further our understanding of how cells survive and adapt to stress in the ER, a condition that has been linked to a variety of human diseases, including diabetes and Alzheimer's disease, as well as viral infection. Understanding how cells cope with this situation will have direct relevance to our understanding of the mechanisms of these diseases. For example, the relationship between obesity and type 2 diabetes has been proposed to be mediated by ER stress and in particular Ire1, a protein whose function will be directly investigated in this study.