Intracellular protein phase separation now is perhaps the most exciting research area in biology. As a major driving force behind the formation of membrane-less cell organelles, protein phase transition impacts many aspects of biological processes and disease pathology. However, the molecular mechanisms by which phase separation influences cell physiology are largely unknown because of the lack of ways to dynamically control the intracellular process.
Here we propose an interdisciplinary approach to develop genetically encoded molecular tools for the reversible control of protein phase separation inside cells. We will leverage a naturally occurring AdoB12-dependent photoreceptor protein CarH. We will examine the feasibility of using the engineered CarH proteins to control the intracellular protein phase separation. The development of those molecular tools will revolutionize our way to interrogate and understand protein phase separation inside cells and thus open up enormous opportunities for studying this prevalent biological phenomenon.