Mechanistic Basis of Spindle Size Control and Scaling

The size and morphology of intracellular structures such as the nucleus, Golgi apparatus, and mitotic spindle dramatically vary between different cell types, yet the mechanisms that regulate the size of these structures are not understood. Interestingly, the size of most intracellular structures scales with cell size, i.e. larger cells tend to have larger nucleus and spindles. So far, many models have been proposed to explain such scaling behavior, but rigorous testing of these models inside the cells is challenging, and often not feasible. To overcome this challenge, we combined the statistical framework of quantitative genetics, with cell biology and biophysics to develop a general methodology to quantitatively examine different models of spindle size control and scaling for the first mitotic spindle in C. elegans. We also use laser ablation technique to quantitatively measure changes in forces under different genetic perturbations. The combination of quantitative genetics with cell biology and biophysics provides a systematic and unbiased method to study mechanisms that contribute to size regulation of intracellular structure and also will give us a deeper understanding of the evolution of these structures.