干细胞的不对称分裂是提供生物多样性的基础，其过程与细胞极性的建立及纺锤体沿细胞极性轴的转向密切相关。LGN蛋白在干细胞不对称分裂中起核心作用，它分别参与两大重要蛋白质复合体Par-mInsc-LGN-Gαi以及LGN-Gαi-NuMA的形成，前者调控细胞极性的建立与维持，后者调节纺锤体的转向。重要的是，LGN调控的这两大细胞不对称分裂蛋白复合体从果蝇到哺乳动物中都是非常保守的。但是由于生化及结构信息的极端匮乏，该过程中关键步骤的作用机制尚不明晰。本项目尝试从蛋白质相互作用以及蛋白结构层次对干细胞不对称分裂中发挥重要功能的LGN及其作用蛋白mInsc，NuMA，Gαi进行深入研究，为干细胞不对称分裂研究提供分子水平的结构信息，进而为理解干细胞不对称分裂过程中关键通路的调控机制提供结构基础。

Asymmetric stem cell division, a fundamental process used to generate cellular diversity during development in metazoan, requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. LGN plays an indispensable role in this process, which is involved in the formation of two important protein complexes: Par-mInsc-LGN-Gαi and LGN-Gαi-NuMA, the former regulates the establishment and maintainess of cell polarity, and the latter controls the mitotic spindle orientation. Importantly, both protein complexes are evolutionary conserved from Drosophila to mammals. However, detailed structural basis of LGN-mediated protein complex assembly is largely unclear. We plan to characterize the biochemical and structural properties of LGN and its related proteins mInsc，NuMA，and Gαi to understand the molecular mechanisms by which LGN connects the Par-mInsc and NuMA-Gαi complexes to coordinate cell polarization and spindle orientation during asymmetric stem cell division.