The centrosome has long been known to promote accurate chromosome and cell division through the regulated nucleation of microtubules. Defects in centrosome function are thought to lead to chromosomal instability, an important factor in the initiation and progression of cancer. The goal of the research proposed here is to investigate the molecular mechanism of centrosome assembly and pericentriolar material (PCM) recruitment in human cells. Studies will focus on the human homolog of the C. elegans centrosome component SPD-2, which has been established in the host lab to play a key role in these processes. I will identify additional components of the PCM and its regulation through biochemical analysis of interacting proteins and genome-wide RNAi screens in human tissue culture cells.
The aims below employ proteomic, cell biological, and genomic approaches, including novel techniques for the study of protein function in human cells. Aim 1: To perform a structure-function analysis of the role of human SPD-2 in centrosome function. Aim 2: To identify hSPD-2-interacting proteins using biochemical isolation. Aim 3: To identify genes required for hSPD-2 localization and centrosome function using high-throughput RNAi screens.
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