The centrosome is a major microtubule-organizing center in animal cells. It consists of a pair of centrioles surrounded by a proteinaceous network of pericentriolar material (PCM). The PCM contains hundreds of proteins and is not a static organization. As the cell enters mitosis, the PCM expands into a micron-sized ensemble in a process termed centrosome maturation. The expanded PCM makes the centrosome a robust microtubule-organizing center and ensures the faithful segregation of chromosomes during mitosis. Although many proteins important for centrosome maturation have been identified at the molecular level, the mechanism underlying PCM assembly and centrosome maturation remains elusive at the organellar level. For example, how is the rapid expansion of PCM achieved? Without an enclosing membrane, what keeps the crowded PCM proteins from dispersing?
We use advanced microscopy, biochemical and cell biological approaches to determine how the centrosome is assembled and functions in cultured mammalian cells and zebrafish embryos. Most recently, we have found that centrosome assembly is regulated by a co-translational protein targeting process. Our recent data also suggest a potential link between liquid-liquid phase separation and centrosome assembly.
Mutations in genes that encode certain centrosomal proteins lead to human disorders such as microcephaly (small brain) and dwarfism. However, it is unclear how centrosomal dysfunction at the cellular level is translated into developmental anomaly at the organismal level. How do defects in an organelle present in most cells cause tissue-specific phenotypes?
Combining powerful genetic and imaging approaches, we use the zebrafish as a model system to determine the pathogenesis of centrosome-related diseases. Our goal is to bridge the knowledge gap between centrosomal dysfunction and disease phenotypes.