纺锤体基质对细胞有丝分裂以及着丝粒组装的调控机制

Mitosis works as the one of most important fundamental process of cell, whose defects will lead to cell apoptosis, developmental abnormality and occur of diseases. The exploration of mitosis not only plays an important role in the scientific research, but also shed lights on the development of society and the health of people. The majority of research in cell division has focused on how spindles and centromeres were assembled during the mitosis, and how MTs of spindles capture the kinetochores of chromosomes for cell division. On the other hand, although the spindle matrix was described as an independent structure associated with spindle and centromeres in the 1960s, whether it is a structural element of the spindle or centromere has remained a subject of debate. Much of the doubt about the spindle matrix stems from a lack of well-defined structure as seen in actin or MTs and the function of spindle matrix was also not quite clear. The purpose of our project is to figure out the detailed function of spindle matrix on spindle and centromere formation, to study the relationship between spindle and centromere, the two most important cellular structures, and to investigate physiological role of the phase transition phenomenon in spindle and centromere formation, which also represents a new angle to study the mechanism of mitosis. And last, targeting genes which could specifically influence cancer cells mitosis, we aim to develop several potential primer compounds to correct defects in centromere assembly and to cure cancer base on the spindle matrix proteins.

细胞的有丝分裂是生物细胞生命活动中最重要的基础进程之一。错误的有丝分裂可导致细胞的凋亡、发育的异常以及疾病的发生。因此有丝分裂的研究不但具有重要的科学价值,而且也具有重大的现实意义与应用价值。在有丝分裂研究中，最核心问题是有丝分裂过程中着丝粒与纺锤体如何被组装以及着丝粒如何准确连接到纺锤体微管上。另一方面在细胞学研究之初,人们就发现了纺锤体与染色体着丝粒之外，还有一层结构特征并不突出但客观存在并独立于纺锤体的特殊结构，并称之为纺锤体基质。我们将具体研究纺锤体基质中对着丝粒组装及着丝粒与微管结合有功能的基因，并且探究着丝粒及其结构组分是否具有相变的特性以及相变在着丝粒组装以及有丝分裂进程中的功能。最终我们将以纺锤体基质蛋白中特异性影响癌细胞有丝分裂的基因为靶点，发掘若干种能矫正有丝分裂中着丝粒组装错误以及治疗癌症的潜在先导化合物。

细胞的有丝分裂是生物细胞生命活动中最重要的基础进程之一。错误的有丝分裂可导致细胞的凋亡、发育的异常以及疾病的发生。因此有丝分裂的研究不但具有重要的科学价值,而且也具有重大的现实意义与应用价值。在本项目研究过程中，发现了能与BuGZ直接相互作用的有丝分裂纺锤体极蛋白Aurora-A能在体内外发生相变。该蛋白在有丝分裂中具有至关重要的作用，及其相变参与调控了中心体成熟、染色体在中期的正确排列，促进有丝分裂纺锤体正确组装。