The Laboratory, headed by Dr. Arshad Desai, is focused on understanding the mechanisms that segregate chromosomes during cell division. Specifically, kinetochores, macromolecular assemblies that form on chromosomes to connect them to spindle microtubules during cell division, are being analyzed. The kinetochore-microtubule connection is central to accurate segregation of chromosomes and prevention of aneuploidy. This interface is also the target of anti-mitotic chemotherapeutic drugs, such as taxol. In the past year, the laboratory has combined functional genomics with proteomics in the early C. elegans embryo to identify nine new kinetochore components. In vivo functional assays are now being employed to define the precise contributions of each component to kinetochore function in C. elegans and these are being extended to analyze selected components in mammals. The group is also studying the mechanisms that specify kinetochore formation at a localized site on chromosomes. The specification event involves formation of specialized chromatin containing a histone H3 variant. Using an unbiased functional genomic strategy, a novel protein involved in chromosomal targeting of this histone variant has been identified and its mechanism of action is being defined.

Chromosome Biology