蛋白质复合物不对称地在细胞特定膜区域上局部聚集（浓缩）是众多生物学过程（包括细胞不对称分裂）的一个基本特性，这也是细胞极性的一个标志性特征。我们前期的发现揭示，果蝇神经干细胞不对称分裂时细胞命运决定因子Numb的底部聚集是由蛋白多位点相互作用引起的液-液相变调控的。然而，目前尚不清楚这种蛋白相互作用引起的相变是否为调控极性蛋白复合物在特定膜区域异位浓缩的一个普遍机制。结合生物化学、生物物理学、以及细胞生物学技术，我们将以保守的核心极性蛋白PAR-3/PAR-6为例探索这一可能。在细胞不对称分裂时，PAR-3/PAR-6异位聚集并形成特异的动态网络调控细胞极性的建立。本研究不仅将为理解细胞极化过程中PAR-3/PAR-6高聚体的形成提供信息，也将为理解细胞极性破坏导致的肿瘤的形成与转移机理提供新视角。

Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes including asymmetric cell divisions (ACD) and is a hallmark of cell polarity. Our previous finding reveals that the basal condensation of cell fate determinant Numb during ACD of Drosophila neuroblasts is mediated by the multivalent protein-protein interaction induced liquid-liquid phase separation. However, it is not known whether such phase-transition-mediated protein condensation on local membrane cortices is a general mechanism for various cell polarity regulatory complexes. With combined biochemical, biophysical and cellular techniques, we plan to test this hypothesis using the conserved core polarity proteins PAR-3/PAR-6 as a paradigm. During ACD, PAR-3/PAR-6 are asymmetrically condensed and form specific and dynamic networks to establish the cell polarity. This work will not only afford information underlying the assembly of PAR-3/PAR-6 complex during cell polarization, but also provide new insight into understanding the mechanism of cancer formation and metastasis induced by disruption of cell polarity.