介导RNAi遗传的无膜细胞器的组分与调控机制研究

无膜细胞器比如P granules、stress granules、P bodies、核仁等是由特定的蛋白质和RNA通过相变自发组装形成的。无膜细胞器参与生殖细胞发育、基因表达调控、环境压力应对等，并与癌症、病毒入侵和神经退行性等疾病关联，然而大多数无膜细胞器的组分、形成和不同无膜细胞器互作调控的分子机制还很不清楚。我们在前期研究中发现，秀丽线虫中新的液滴状无膜细胞器Z granules和空间有序的三无膜细胞器结构PZM介导了RNAi遗传，并影响后代的生殖细胞发育。本项目将在上述研究的基础上，通过生物化学和遗传筛选等手段研究PZM组分、发育过程中形成和互作调控的分子机理，以及这些形成和互作的异常对小RNA信号通路的影响。本研究将为无膜细胞器的调控机理提供新的理论见解，并为相关疾病治疗提供潜在的依据。

Membrane-less organelles such as P granules, stress granules, P bodies and nucleoli form by spontaneous self-assembly of specific proteins and RNAs through phase separation. Membrane-less organelles play important roles in germ cells development, gene expression regulation, environmental stress response, and are tightly linked to cancer, virus invasion and neurodegenerative diseases. However, the components and the molecular regulatory mechanisms behind formation and interaction of most membrane-less organelles are poorly understood. Previously, our work shows that new liquid droplet membrane-less organelle termed Z granules and spatially ordered tri-membrane-less organelles termed PZM mediate RNAi inheritance, and affect germline development in progeny. Based on above mentioned work, harnessing biochemical and genetic screen approaches, current project will study the components of PZM and molecular regulatory mechanisms of formation and interaction of PZM during development, and how aberrant formation and interaction affect small RNA pathways. This work will gain new insights into regulatory mechanisms of membrane-less organelles, and potentially benefits related disease treatment.