Cells are organized into membrane-bound and membraneless structures referred to as condensates. Condensates contain concentrated biomolecules, including protein and nucleic acid, and are suggested to play a role in nearly all biological processes. The focus of my lab is to understand the molecular details of condensates using quantitative imaging of condensates in living animals and in vitro models to understand the physiology and pathophysiology of these membraneless structures.
Approach: We couple observations in live cells with genetic, biochemical, biophysical, and theoretical analysis. We use techniques including super-resolution microscopy, quantitative live cell imaging, biophysical measurements, single molecule imaging, and modeling to understand condensate assembly at the molecular level.
Germ granules in development: Germ granules are membrane-less structures assembled by RNA-protein (RNP) complexes found in the germ cells, embryos, oocytes, and sperm of animals. Germ granules have been a powerful model to understand the properties and functions of membrane-less condensates. The investigation of germ granules has revealed a diverse array of functions, highlighting their significance in germline development, stress response and epigenetic inheritance.
The nematode Caenorhabditis elegans, a widely studied model organism, offers exceptional opportunities for understanding the formation and functionality of germ granule condensates. We are utilizing the wide range of tools available for C. elegans including live cell super-resolution imaging and analysis in an intact animal and the extensive genetics tool box including CRISPR and RNAi to understand germ granules at the molecular level.
Exploring Condensate Substructure: Impact of Material Properties on Function and Regulation
Cellular condensates often exhibit intricate substructures. Building upon previous research, we have discovered that germ granules in C. elegans consist of a dynamic liquid-like core surrounded by less dynamic solid-like clusters. The solid clusters adsorb to the liquid surface, reducing surface tension and preventing coarsening—a phenomenon known as Pickering stabilization, originally described in materials science over a century ago. Leveraging both in cellular and reconstituted models, we aim to study the influence of condensate substructure and material properties on condensate behavior. Through these studies, we seek to unravel fundamental insights into the relationship between condensate organization and cellular function.
Condensation and enzymatic activity: Condensates contain enzymes that modify proteins, small molecules, and nucleic acids. In artificial and in vitro reconstituted systems, condensates can both enhance and inhibit enzyme activity. Disruption of enzymes can also alter the formation, morphology, and material properties of condensates in cells. Using RNA processing enzymes enriched germ granules, we will examine how condensation regulates enzymatic activity and, conversely, how activity can regulate condensation.
200 nm microspheres in unmodified (left)
or enzymatically modified (right) condensates.