The many phases of a cell

Abstract: Cells routinely orchestrate reactions, interactions, and transport amongst billions of biomolecules in a crowded environment to perform the diverse tasks that underpin life. Rather than occurring in a well-mixed milieu, biomolecules self-organize into dozens of membrane-lacking compartments called condensates that enable key biological functions and are aberrant in disease. I will begin my talk by introducing phase transitions as an emerging paradigm underlying condensate assembly and function in cells. I will then highlight challenges that limit our understanding of condensates, which unlike equilibrium oil-water mixtures, are highly multicomponent, multiphasic biomolecular assemblies that are driven out of equilibrium by fluxes and forces. Through specific examples, I will propose an interdisciplinary and collaborative approach that advances our understanding of condensates by bridging non-equilibrium thermodynamics, physical chemistry, and soft matter physics in the cellular context. In the first part of my talk, I will discuss past/ongoing work that links condensates to regulation of gene expression and focus on the emerging role of non-equilibrium RNA synthesis in genome/nuclear organization. In the second part, I will discuss complementary efforts to build quantitative physical frameworks that enable prediction and design of emergent multiphase behavior in multicomponent fluids. I will conclude with a brief summary and discussion of exciting future directions and opportunities for translation.