CCDC50在抗病毒天然免疫中的功能和机制研究

天然免疫是一种非特异性的宿主抵抗病原微生物入侵的免疫反应,被认为是机体抵御病原体感染的第一道防线。随着近几十年的研究，人们对天然免疫系统愈发了解，已经发现并鉴定出天然免疫反应的信号转导因子和关键调控因子，然而某些调控因子的结构和功能机制依然不清楚，此外细胞的抗病毒免疫信号通路的精密调控机制还有待于进一步深入探究。我们前期的工作利用CRISPR/Cas9文库在免疫细胞中进行全基因组水平的大规模无偏差的筛选，发现了一些参与调控天然免疫反应的新型基因。因此本课题旨在对筛选出的新型调控因子CCDC50做进一步的功能验证和机制探究。我们发现CCDC50的泛素链结合功能和酪氨酸磷酸化特性积极地调节了RIG-I/MDA5/VISA复合体的活性和先天免疫反应。本项目将深入研究CCDC50在抗病毒天然免疫中的调控作用和生理意义，并寻找新的抗病毒作用靶点，为开发广谱性的抗病毒感染药物做探索性的研究。

Natural immunity is a non-specific host immune response to resist invasion of pathogens. It widely exists in most of human cells and is considered to be first defense against infection. With recent decades of study, people have an increasingly understanding of natural immune system and have also identified the signal transduction factors and key regulatory factors. However, the functions and the mechanisms of regulatory factors are still unclear. Moreover precise regulatory mechanism of antiviral signaling pathways also needs to be further explored. In our previous work, we used second generation library of CRISPR/Cas9 to carry out genome-wide large-scale unbiased screen in immune cells and found some new hits involved in the regulation of natural immune response. Therefore, this study aims to further investigate the functions and mechanisms of the new regulatory factor CCDC50.We found that the function of CCDC50 to bind ubiquitin chains and tyrosine phosphorylation characteristics actively regulates the activity of RIG-I/MDA5/VISA complex and innate immunity. This project will verify and elucidate the regulatory functions and physiological significances of CCDC50 in antiviral innate immunity. We will explore potential antiviral target and do exploratory research for the development of broad spectrum of antiviral drugs.