纺锤体装配与染色体向子细胞中平均分配的调控机理研究

有丝分裂纺锤体的正确装配对于染色体向子细胞中的平均分配至关重要。在细胞增殖过程中，中心体在S期完成复制，在有丝分裂期成熟并参与中期纺锤体的装配。很多肿瘤细胞都伴随着纺锤体形态的异常和子代细胞染色体组的不稳定性。在本项目中，我们将探索细胞有丝分裂过程中中心体所介导的纺锤体动态装配调控以及由纺锤体所介导的染色体向子细胞平均分配的过程和机理。鉴于纺锤体是一种结构复杂的无膜细胞器，我们将会筛选中心体和纺锤体上具有相分离能力的结构性和调节性蛋白质，确定蛋白质的相分离是否以及如何参与调控纺锤体的装配及动态性维持等生物学过程。我们将利用单细胞、3D细胞培养及转基因果蝇等系统，通过进行相关作用因子筛选和翻译后修饰分析等手段，探索纺锤体蛋白质的相分离和细胞周期蛋白激酶、微管结合蛋白等重要纺锤体装配调控蛋白之间的相互协同关系，最终阐明纺锤体装配和染色体分离的调控机理，并为纺锤体相关疾病研究提供线索。

The accurate assembly of mitotic spindle is critical for the faithful distribution of duplicated chromosomes of mother cells into their daughter cells. During the process of cell proliferation, the centrosomes complete replication in S phase, mature in mitosis and participate in spindle assembly. Many tumor cells are associated with abnormal assembly of the mitotic spindle and instability of the progeny cell genome. The mechanisms that regulate centrosome maturation and spindle microtubule dynamics remain largely unknown. Since the spindle is the structural complex membraneless organelles, we in this project aim to screen centrosome and spindle localized structural and regulatory proteins with phase separation ability, determine whether and how protein phase separation is involved in the regulation of critical cell cycle events, including spindle assembly, spindle dynamic maintenance and chromosome distribution. Taking advantages of single cell, 3D cell culture and transgenic Drosophila systems, we will explore the cross-talk mechanisms between the phase separation of centrosome proteins and cell cycle kinases system and explore the collaborative relationships between centrosome proteins and spindle assembly regulatory proteins including tubulin binding proteins. These studies will certainly help us to elucidate the regulation mechanism of spindle assembly and chromosome distribution during cell cycle, and contributes to the pathogenesis of spindle-related genetic diseases.