Chromosome segregation accuracy relies on the proper attachment of chromosomes to microtubules, during the process of cell division. Chromosome-microtubule attachment is facilitated by a macromolecular structure called the kinetochore. The extent to which naturally occurring variations in kinetochore genes can promote chromosomal instability is not clear, although strong evidence for such predisposition exists among DNA damage repair pathway genes. To address this knowledge gap, the PhD student will identify potentially harmful variants in chromosome segregation genes using bioinformatics and structural biology tools. To identify variants, the student will use data available in the ELGH, Gnomad, Centenarian and Biomuta databases. To predict those that are harmful, the student will use published structures of kinetochore proteins. To investigate the impact of the variants, the student will introduce the variants in human cells and use cutting-edge super-resolution and deconvolution live-cell microscopy tools to probe changes in chromosome-microtubule attachments induced by variant protein expression. The findings will provide the first insight into genetic variations that individually or jointly poised to promote chromosome instability and premature cellular ageing.