Cell division, the accurate transfer of genetic information from one cell generation to the next is the molecular basis of life. To achieve high fidelity genetic transfer, cell division involves highly orchestrated events such as 1. chromosome condensation 2. formation of a stable spindle assembly 3. physical attachment of chromosomes to the spindle microtubules through a molecular assembly called the kinetochores 4. movement of sister chromatids towards the opposite spindle poles and 5. the successful completion of cytokinesis. A number of mitotic molecular machines involving extensive network of protein-protein interactions are implicated in above mentioned steps towards achieving accurate cell division.
Understanding the molecular mechanisms of accurate chromosome segregation is crucial as defects in segregation, which is a source for chromosome instability (CIN, resulting in the abnormal chromosomal content of a cell) has direct implications in cancer. Mitotic protein kinases and number of kinetochore-associated proteins contain mutations in several cancer types. Inappropriate cell division, in addition to its role in cancer, is also implicated in Down syndromes and Alzheimer’s.
Our lab is interested in understanding the molecular mechanisms of accurate cell division by structurally characterizing protein complexes that play a crucial role in achieving accurate cell division. These structural studies will allow us to understand how specific protein-protein interactions are translated into the regulation of cell division and would allow us to explore possibilities of targeting specific KT proteins in fighting cancer.