Deciphering pericentriolar material architecture and assembly principles using sub-diffraction imaging.

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Centrosomes are composed of a pair of 9-fold symmetric barrel-shaped structures coined centrioles, which are surrounded by many proteins collectively referred to as pericentriolar material (PCM). PCM is responsible for several aspects of centrosome biogenesis and function including the nucleation and anchoring of microtubules. The mitotic spindle is an essential cellular structure that physically carries out the task of accurately transmitting chromosomes to progeny cells as they grow and divide. The two poles of the mitotic spindle are organized by centrosomes and without properly functioning centrosomes, the mitotic spindle will not form correctly. Therefore, in the absence of functional centrosomes, chromosomes would not segregate accurately to each daughter cell leading to a condition called aneuploidy that can cause devastating diseases like cancer. Traditionally described as amorphous, we have recently discovered using super-resolution microscopy that the PCM is much more ordered than generally thought. In particular, we found that different PCM proteins occupy distinct spatial domains in line with their functions in the regulation of centrosome biology. The major objective of this proposal is to build on this exciting new discovery and generate high-resolution spatial and temporal maps of the human centrosome. In addition, we will study the contribution of known centrosome proteins in the organization of centrosome domains and identify novel regulators of this process. Overall, this work will lead to a better mechanistic understanding of centrosome organization and assembly and how they are regulated during the cell cycle.