Cell cycle regulation of centrosome biogenesis

How does a cell maintain the correct number of organelles? In the case of centrosomes, this is critical for genetic stability. Centrosome duplication is tightly controlled by the Cell Cycle Oscillator (CCO), a network of regulators whose oscillatory activity controls the cell division cycle. However, the centrosome duplication cycle can be uncoupled from the CCO, presenting a mystery: if the CCO is critical to regulating centrosome duplication, how can centrosome duplication occur without it? I will develop centrosome-targeted FRET biosensors to measure the activity of key cell cycle regulators, providing a readout of local centrosomal CCO dynamics. I will combine this with assays of centrosome biogenesis to correlate local CCO regulation with centrosomal events, and investigate the mechanisms underlying this by acutely inhibiting key CCO components. Finally, I will investigate how centrosome duplication continues without global CCO oscillations. I will use the centrosome-targeted biosensors to test whether local oscillations in CCO activity continue in these conditions, and test what regulators are necessary for centrosome duplication to continue. This work will provide insight into how the cell cycle is coupled to the centrosome cycle, which ultimately ensures faithful cell division.