Understanding the molecular mechanisms of kinetochore-microtubule attachments.
The Dileep Varma Lab
Accurate chromosome segregation requires the successful and error-free association between kinetochores of the chromosomes and the plus-ends of microtubules of the mitotic spindle. Errors in this event lead to chromosome loss and aneuploidy which is a hallmark of cancer cells and leads to birth defects during human embryonic development. Research in the past several years has provided conclusive evidence that the Ndc80 kinetochore complex is crucial for this process but we still do not clearly understand how this complex is coupled to dynamic microtubule plus-ends during mitotic metaphase and anaphase in vertebrate cells.
We also do not have an accurate picture of how the kinetochore microtubule attachment mechanisms are coordinated seamlessly with the spindle assembly checkpoint, the essential surveillance mechanism that controls the fidelity of the chromosome segregation process. Studying the intricacies of these mutually linked phenomena will not only provide valuable information pertaining to the understanding of cancer initiation and progression but also lead to the identification of novel biomarkers and targets which in turn is likely to yield better diagnostic and therapeutic tools to combat this dreaded disease.