项目来源

国家重点研发计划(NKRD)

项目主持人

周兆才

项目受资助机构

复旦大学

项目编号

2020YFA0803201

立项年度

2020

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

947.00万元

学科

发育编程及其代谢调节

学科代码

未公开

基金类别

未公开

关键词

信号转导 ; 信号通路 ; 分子机制 ; 相分离 ; Signal transduction ; Signal pathway ; Molecular mechanism ; Phase separation

参与者

汪雯佳

参与机构

同济大学；华中科技大学；中国科学院分子细胞科学卓越创新中心

项目标书摘要：本课题主攻组织器官生长和尺寸控制的信号基础研究，主要通过遗传学等筛选策略系统鉴定肝、肠等组织器官生长和尺寸控制的关键信号和因子，并利用模式动物、生化结构和高通量测序等前沿技术手段，揭示组织器官生长和尺寸控制过程中关键信号的诱发与转导机制。在课题开展的前两年，本课题组成员在Hippo信号通路调控器官稳态、组织损伤修复及肿瘤生长等方面取得良好进展，共发现5种与Hippo、mTOR等通路相关的组织器官调控因子，并揭示这些因子响应炎症因子、放化疗等刺激条件下调控尺寸信号的分子机制。同时，正在加速推进肠道类器官研究体系及新型的细胞互作体系的体内外评价，特别是基于邻近标记技术的细胞间直接互作体系取得突破性进展。在此基础上，本课题将继续按照预设目标和进度开展相关功能筛选，发现与肝、肠器官生长和尺寸控制的新型调控因子，揭示这些因子的信号感知及调控机理，为课题二和课题三提供研究基础。

Application Abstract: The focus of topic one is characterization the signal transduction cascades in mediating the tissue development and organ size control.Specifically,we aim to systemically identify the upstream signals to trigger,as well as the mediators to initiate the activation of Hippo and mTOR signaling,as both of which play crucial roles in tissue development and organ size control.Technically,we will apply a wide range of systems including model organisms,structural biology,and novel sequencing strategies to dissect the underlined mechanisms,providing the comprehensive regulatory network in controlling the organ size of both liver and intestine.In the first two years of this five-year project,we achieved great progresses in Hippo signaling regulation at diverse layers and established multiple interrelationships between dysregulation of key factors and diseases.We identified five transcriptional factors related to Hippo or mTOR signaling pathway regulating tissue development and organ size control and deciphered the mechanism.In addition,we have set up several genetic platforms and will start to screen regulators of both liver and intestine development and organ size control in vivo.Taken together,we have fully finished our goals as planned and are moving fast to the next step based on our progresses achieved in these two years.

项目受资助省

上海市

联系人信息

汪雯佳：wangwj@fudan.edu.cn