Robert W. Vaughan Lecture in Chemical Engineering

In this talk I will discuss our work to understand and engineer intracellular phase transitions, which play an important role in organizing the contents of living cells. Membrane-less RNA and protein rich condensates are found throughout the cell, and regulate the flow of genetic information. We've shown that liquid-liquid phase separation (LLPS) underlies the assembly of these structures. LLPS driven by intrinsically disordered protein regions (IDRs) explains many condensate features, for example the internal subcompartments of the nucleolus, which has important consequences for sequential ribosomal RNA processing. Our lab has developed a suite of new approaches, which use light to enable spatiotemporal control of intracellular phase transitions, allowing us to engineer the assembly and disassembly of these structures within defined subregions of the cytoplasm and nucleus. We are now using these tools to quantitatively map intracellular phase diagrams for the first time, providing unprecedented access to the biophysical principles underlying RNP condensate self-assembly. This approach has also begun to yield rich insights into the link between intracellular liquids, gels, and the onset of pathological protein aggregation.