The cell cycle is driven by the tightly-choreographed activity of cyclins and their catalytic partners, cyclin-dependent kinases (CDKs). While the roles of these complexes in cell cycle progression have been thoroughly characterized, more recent work has identified distinct functions of cyclins and CDKs in cellular processes such as differentiation, DNA repair, and metabolism. I am interested in understanding how cell size is regulated, and how a cell knows what size to be. In mammals, cell size is largely controlled through the coordination between growth rate and time spent in the G1 phase of the cell cycle. However, we have recently shown that CDK4, acting in G1, asserts a unique influence by which it dictates the size to which a cell aims to grow, or its target size, an ability not shared by other G1 CDKs. Inhibition of CDK4 results in a population of cells with uniformly increased size, while increased CDK4 activity causes cells to be uniformly small. To investigate the physiological implications of this phenomenon, we have turned to the tractability and wealth of genetic tools offered in C. elegans. Knockdown of the C. elegans CDK4 homolog
cdk-4 or its conjugate cyclin
cyd-1 is sufficient to increase the size of both the nucleus and nucleolus in seam cells, used here as a proxy for cell size due to the scaling of these organelles with cell size through development. Preliminary work also suggests that while overall metabolism is increased, fat stores are depleted in worms with reduced CDK-4 activity. We seek to understand the mechanisms behind this accumulation of cell mass, and the consequences of our observed changes in metabolism on the adult worm.