The role of centromere proteins in centromere assembly, chromosome instability, and cancer

我们的遗传信息被组织成紧凑的结构，在我们的细胞中称为染色体。每个人类细胞有46条染色体。这些染色体的拷贝过多或不足都会导致遗传失衡，这往往会导致严重的临床问题，如唐氏综合症、癌症、胚胎死亡和一系列其他综合征。因此，研究细胞分裂时染色体的确切数量如何在子代细胞中分布的过程是一个重要的研究领域。我们的实验室重点研究了染色体的一个关键结构，即着丝粒，它决定了这一过程是如何控制的。本项目旨在利用小鼠靶向基因突变技术详细研究着丝粒的性质。在这些小鼠中，通过精确控制的突变过程，产生特定着丝粒蛋白的单个基因的功能被破坏或修改。然后可以非常详细地分析这种突变对动物发育和染色体分裂的影响。其结果将是我们对不同着丝粒蛋白功能的理解显著增加，这是进一步提高我们对包括癌症在内的一些人类最常见疾病的病因学知识的关键。

Our genetic information are organised into compact structures known as chromosomes in our cells. Each human cell has 46 chromosomes. Excess or insufficient copies of these chromosomes will cause genetic imbalance that often results in serious clinical problems such as Down syndrome, cancer, embryonic death, and a host of other syndromes. The study of the process of how the exact number of chromosomes is distributed amongst daughter cells when cells divide is therefore an important area of research. Our laboratory has focused research on a key structure of the chromosome known as the centromere that determines how this process is controlled. The present project aims to study the properties of the centromere in detail using the technique of targeted gene mutation in mice. In these mice, the functions of individual genes that make specific centromere proteins are destroyed or modified through a precisely controlled mutation process. The effects such mutations have on the development of the animals and on chromosome division can then be analysed in great detail. The outcome will be a significant increase in our understanding of the functions of the different centromere proteins, an understanding that is key to the further advancement of our knowledge on the aetiology of some of the most frequently seen disease conditions in humans, including cancer.