Proximity-Labelling Proteomics Reveals Novel Regulatory Mechanisms of Condensate Dynamics

Biomolecular condensates concentrate biomolecules in the cell, often formed by the physical process of liquid-liquid phase separation. By enriching specific biomolecules, biomolecular condensates can increase or decrease biochemical reactions, buffer protein concentrations, sense environmental changes, and provide mechanical forces. To study condensate function, we employ proximity-based labeling methods (BioIDor APEX) to determine condensate proteomes. Biomolecular condensates are dynamic and also metastable. Aberrant phase transition underlies the pathogenesis of neurodegenerative diseases. We apply quantitative mass spectrometry to measure changes in proximal interactions associated with condensate formation and aberrant phase transition. I will share our ongoing studies of cytosolic biomolecular condensates formed during stress, called stress granules (SGs) and TDP-43 (TARDBP) condensates.