纺锤体检验点机制在有丝分裂中监测动点与微管的连接，并且阻止后期的进入直到所有的染色体都成功地实现了稳定的双级定向连接。作为有丝分裂检验点的关键激酶，TTK（Threonine and tyrosine kinase）调控着有丝分裂的各种层面。抑制TTK激酶活性会导致纺锤体检验点的失控，TTK激酶因而成为治疗癌症的重要靶蛋白。因此，筛选专一的TTK激酶的抑制剂已成为生物学领域的热门课题。本项目将采用虚拟筛选的方法开发TTK激酶抑制剂，通过分子模拟对接和构效关系分析，深入研究纺锤体检验点的机制。借助生物信息学和化学生物学的方法研究有丝分裂激酶和检查点蛋白质功能的工作，为深入研究有丝分裂检验点激酶级联反应的动力学和可塑性奠定基础。TTK激酶化学探针等新技术的发展使我们能够在纳米尺度下揭示染色体分离保真性的分子机制奠定基础。

The spindle assembly checkpoint surveys proper attachment of chromosomes to the mitotic spindle and effectively suppresses erroneous chromosome segregation by delaying mitotic progression until proper spindle-chromosome interactions have been established. As a key protein kinase in the regulatory hierarchy of mitosis, threonine and tyrosine kinase (TTK) has been proven to regulate almost every aspect of mitosis. TTK is an attractive target for therapeutic treatment of cancers nowadays for disruption of TTK function induces the blockade of the spindle assembly checkpoint. So, discovering potent and selective small-molecule inhibitors of the TTK has become one of the most active fields in biological researches. In this project, we will explore a virtual screening-based inhibitor approach targeting the key spindle checkpoint gene TTK to investigate the suitability of the spindle checkpoint as a therapeutic target in vitro and in vivo.. This project on the mitotic kinases and checkpoint proteins with bioinformatics and chemical biology methods, will provide novel insights into a better understanding of kinase cascade in mitotic checkpoint dynamics and plasticity．The advancement in specific chemical probes of TTK enables us to visualize spatiotemporal gradient of kinase activity at nano-scale and understanding about the surveillance mechanism that ensures faithful chromosome segregation.