Decoding and Targeting Protein-RNA Condensates

In biological cells, multivalent disordered RNA/DNA-binding proteins form dynamic membraneless-condensates that play essential roles as hubs for intracellular storage and signaling. Examples include: the nucleolus, stress granules (SG), processing bodies (P-bodies or PB), transcription factories, PML bodies, heterochromatin domains, and para-speckles. In our laboratory, we investigate the most fundamental properties of these bio-condensates, including their structure, dynamics, composition, and fluid (transport) properties, which are critical to their cellular functions. Our studies will lay the ground work to therapeutically target bio-condensates that are associated with many human diseases including neurodegenerative disorders and certain types of cancers.

Correlative Optical Tweezers and Fluorescence Microscopy

We are developing novel multi-parametric methodology featuring correlative single-molecule fluorescence microscopy, optical tweezers, and microfluidics, a combination that will robustly quantify the rheology of nascent and matured nucleoprotein condensates in nano-to-microscale. We will employ this toolbox to dissect and target sequence-encoded molecular interactions that drive viscous-to-elastic transition of protein-RNA droplets.

Transcription Factor Condensates and Chromatin Compartments

We are employing an integrative experimental and computational approach to dissect the role of liquid-liquid phase separation in DNA condensation and transcription regulation at specific DNA sites.