Compartmentalization in cells is central to accomplishing diverse and simultaneous biomolecular interactions. In addition to membrane-bound organelles, cells organize many biochemical processes in membrane-less compartments. It has recently emerged that those membrane-less organelles are liquid droplets condensed from the cytoplasm/nucleoplasm through liquid-liquid demixing. It is however not clear what are the driving forces for phase transitions and how droplets maintain distinct functional and physical identities. With Whi3, an RNA-binding protein that contains a polyQ-expansion, we show that specific targeting RNAs can drive protein droplet formation at physiological conditions. RNAs can also alter the viscosity of droplets, their propensity to fuse, and the exchange rates of components with bulk solution. Different targeting transcripts impart distinct biophysical properties of droplets, indicating mRNA can bring individuality to assemblies. Furthermore, irreversible aggregates are observed in aged droplets indicating a mechanism that underlies the formation of pathological aggregates and are in line with the observation that RNA binding proteins with disordered prion-like domains are often associated with degenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases.
Dr. Huaiying Zhang has a longstanding interest in applying engineering principles to address biological issues. During her Ph.D. in chemical engineering at McGill University, she examined the diffusion and electrophoresis of lipopolymers in lipid bilayers with a combination of experimental and theoretical tools. During her post-doc at Dartmouth, she studied how principles of phase transition are applied in cells to create RNA granules, liquid droplets composed of RNAs and RNA-binding proteins. She discovered that instead of taking a free ride, RNAs actually drive RNA-binding proteins to form liquid droplets and tune droplet physical properties including viscosity, ability to fuse and exchange component with the surroundings. The focus of her independent research program will be intracellular phase transitions