Projects

Biomolecular condensates, which lack a lipid membrane and include nucleoli, P-bodies, and stress granules, are formed through phase separation driven by multivalent macromolecular interactions involving intrinsically disordered proteins/regions (IDPs) and nucleic acids. These condensates create microenvironments that can respond rapidly to environmental changes. They can assemble and dissolve quickly to support diverse cellular functions, and may also transition into solid aggregates and fibrils, potentially contributing to neurodegenerative diseases, cancer, and metabolic disease. However, the dynamics of biomolecular condensates—especially under non-equilibrium conditions—have not yet been comprehensively studied. This project aims to leverage our advanced non-equilibrium detection technologies to systematically investigate the complete life cycle of biomolecular condensates, from rapid initial cluster formation to gradual aging processes, and to connect these states to cellular functions. We aim to determine whether these processes or states follow universal or context-specific mechanisms and to explain them using possible physical models. 

Biomolecular condensates are membraneless cellular compartments that selectively enrich macromolecules and create distinct microenvironments. Many enzymes function within biomolecular condensates. A major open question is how these environments modulate enzyme activity—through changes in local concentration, diffusion and transport, material properties such as viscosity, and shifts in conformational or allosteric states.

We apply quantitative single-molecule approaches to connect enzyme structure, dynamics, and kinetics in condensate versus dilute environments. We integrate complementary measurements across timescales, capturing conformational state switching, reaction dynamics under non-equilibrium conditions, and molecular mobility and permeability within dense phases. A longer-term goal is to translate key assays to cellular contexts in order to probe enzyme behavior in spatially confined, dynamic compartments.