Elucidating the structure of biomolecular condensates using cryo-ET

Biomolecular condensates are compartments in eukaryotic cells that concentrate macromolecules in discrete foci without a surrounding membrane.  Examples include cytoplasmic P bodies associated with RNA metabolism, promyelocytic leukemia nuclear bodies involved in transcription and anti-viral responses, signaling clusters in T cell activation, HP1 clusters in heterochromatin organization, and transcriptional assemblies involved in gene regulation.  The behaviors of these compartments suggest that they may form through liquid-liquid phase separation of multivalent proteins and RNA. I am developing and applying cryoelectro- tomography (cryo-ET) methods to understand the molecular organization of biomolecular condensates, in particular those involved in chromatin organization.  My goal is to understand how molecules interact are spatially organized in natural condensates in cells and in reconstituted condensates in vitro, and ultimately relate this organization to biochemical and cellular functions.