Centrosome biology in health and disease
We are fascinated by cell division, a visually stunning and biochemically complex process, which enables the accurate transmission of genetic information (encoded in chromosomes) from one cell generation to the next. By capturing and segregating chromosomes equally into daughter cells, the mitotic spindle plays a pivotal role in this process. Each pole of the bipolar spindle associates with a centrosome, a membraneless organelle, which comprises a pair of conserved cylindrical structures called centrioles and a protein-rich matrix of ~150 proteins. Centrosomes nucleate and organise microtubule filaments that are fundamental not only for mitotic spindle formation and chromosome segregation, but also for orchestrating essential processes such as trafficking, secretion, migration, polarity establishment, and primary cilium assembly. In line with these diverse roles, mutations in centrosomal genes cause a variety of developmental disorders including primary microcephaly, primordial dwarfism and ciliopathies, whereas abnormal centrosome number and structure are considered a hallmark of cancer.
By studying centrosome function and composition across cell and tissue types our group wants to understand how centrosome abnormalities impair development and contribute to tumourigenesis. We focus on microcephaly- and dwarfism-associated genes because they serve as a great starting point for deciphering tissue-dependent crosstalk mechanisms between centrosomes and the cell cycle. Our lab is part of an exciting collaboration that will develop new tools and methods to dissect the roles of intrinsically disordered proteins and their interactions in mitotic regulation. We interrogate these important questions using a multidisciplinary approach that combines molecular and cell biology techniques, quantitative proteomics, gene editing and super-resolution microscopy.
To find out more visit our lab website; https://gergelylab.com