Hedgehog信号通路与应激颗粒的交互作用及其功能研究
结题报告
批准号:
31970755
项目类别:
面上项目
资助金额:
60.0 万元
负责人:
金志刚
依托单位:
学科分类:
细胞外微环境与细胞间通讯
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
金志刚
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中文摘要
出生缺陷是导致婴幼儿死亡和先天残疾的主要原因,目前我国发生率约5.6%,其中环境是重要诱因。Hedgehog(Hh)信号通路在胚胎发育中发挥了重要作用,其异常导致多种出生缺陷。然而胚胎微环境如何通过调控Hh信号通路来影响胚胎发育,目前尚不明确。在环境压力下通过液相分离形成应激颗粒(Stress granules, SG)是细胞的一种环境应答方式。我们预实验发现一系列Hh信号蛋白被转运至SG,提示SG通过招募Hh信号蛋白调控了该信号通路。其中部分蛋白还调控了SG组装/解聚动态,提示Hh信号通路与SG的互作。据此,我们将在不同蛋白水平考察Hh信号通路与SG的互作机制,并利用爪蟾和鸡胚神经管发育模型,研究Hh信号通路与SG的功能互作,揭示SG传递胚胎微环境信号于Hh信号通路进而影响胚胎发育的作用机制,从而阐明两者互作在出生缺陷发病机理中的重要作用,并为其预防和治疗方案提供新的思路和重要理论依据。
英文摘要
Birth defects contribute substantially to infant mortality and congenital disability, they occur in about 5.6% newborns in China now, and environmental factors are the leading cause. Hedgehog (Hh) signaling pathway serves fundamental roles in many embryonic developmental processes. Its dysregulation was found to be responsible for many syndromes of birth defects. A major unsolved question is how it is regulated by embryonic microenvironment. Environment-stimulated formation of stress granules (SG) via liquid-liquid phase separation is one of the major ways utilized by the cells for response to environmental stress. Our pilot study showed that several Hh signaling proteins are recruited to SG, indicating that SG might regulate Hh signaling. Meanwhile, some of Hh signaling proteins also regulate SG condensation/dissolution dynamics, indicating their mutual interaction. Thus, we aim to investigate the molecular mechanisms and outcomes of Hh-SG interaction at different protein levels. Using Xenopus and chick embryos as animal models, we will focus on the functional interaction between Hh signaling and SG during neural patterning to verify our hypothesis that SG relays environmental signals to Hh signaling and embryonic developmental processes. Overall, our study will uncover the importance of Hh-SG interaction in the etiology of Hh signaling-associated birth defects, and provide a rationale for development of preventive and therapeutic strategies.
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Photoelectrochemical Aptasensors Constructed with Photosensitive PbS Quantum Dots/TiO2 Nanoparticles for Detection of Kanamycin.
用光敏 PbS 量子点/TiO2 纳米粒子构建的光电化学适体传感器用于检测卡那霉素。
DOI:10.1021/acs.langmuir.0c03593
发表时间:2021
期刊:Langmuir : the ACS journal of surfaces and colloids
影响因子:--
作者:Yichen Xing;Xiaoxiao Chen;Boxing Jin;Piaopiao Chen;Chaobiao Huang;Zhigang Jin
通讯作者:Zhigang Jin
DOI:10.1021/acs.chemmater.1c03837
发表时间:2022-03
期刊:Chemistry of Materials
影响因子:8.6
作者:Hui-Min Zeng;Boxing Jin;Wei-Hong Wu;Chao Wang;Zhan-Guo Jiang;Zhigang Jin;Cai‐Hong Zhan
通讯作者:Hui-Min Zeng;Boxing Jin;Wei-Hong Wu;Chao Wang;Zhan-Guo Jiang;Zhigang Jin;Cai‐Hong Zhan
DOI:10.13488/j.smhx.20200708
发表时间:2021
期刊:生命的化学
影响因子:--
作者:张梦;蒋莹佩;金志刚
通讯作者:金志刚
DOI:--
发表时间:2022
期刊:生物医学
影响因子:--
作者:周钰林;宋振;金志刚
通讯作者:金志刚
DOI:10.3389/fmicb.2019.03033
发表时间:2020
期刊:Frontiers in Microbiology
影响因子:5.2
作者:Zhilong Wang;Wanhang Lu;Yiling Zhang;Feng Zou;Zhigang Jin;Tiejun Zhao
通讯作者:Tiejun Zhao
Hedgehog信号通路蛋白Rusc2对神经模式形成的调控
  • 批准号:
    LY21C120001
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2020
  • 负责人:
    金志刚
  • 依托单位:
国内基金
海外基金