Phase separation drives nucleolar assembly and size control

The Weber lab uses quantitative live-cell imaging and physical modeling to investigate the mechanisms governing spatial organization in cells. Recent work focuses on the nucleolus, a large membraneless organelle responsible for ribosome biogenesis. By genetically manipulating the size of C. elegans embryos, we identified a concentration threshold below which nucleolar components remain dissolved in the nucleoplasm and above which they condense to form the nucleolus. Moreover, the size of the nucleolus scales with the size of the cell. Finally, despite nonequilibrium activity in the cell, the kinetics of nucleolar assembly are consistent with thermodynamic models of first-order phase transitions. Our results indicate that the nucleolus assembles by liquid-liquid phase separation of the nucleoplasm. Given the ubiquity of membraneless organelles in both the nucleoplasm and cytoplasm of eukaryotic cells, we are currently investigating whether bacteria also use phase separation as a mechanism for compartmentalization.