Sequence determinants of protein phase separation: Biophysical principles and synthetic biology applications
Membraneless organelles are intracellular compartments with important biological functions, ranging from stress response to regulation of gene expression. These compartments lack an enclosing membrane, instead forming via liquid-liquid phase separation arising from multivalent interactions. Membraneless organelles are often enriched in intrinsically disordered proteins (IDPs), which have been identified as key drivers of phase separation. In this talk, I will first present our recent work to understand the sequence features responsible for phase separation of a prototypical IDP, the arginine/glycine-rich RGG domain from LAF-1. We identified three key features responsible for phase separation of this RGG domain: a short conserved sequence, charge patterning, and arginine-tyrosine interactions. These findings are the result of a collaboration (with Jeetain Mittal, Lehigh University) combining experiments with predictive simulations. In the second part of my talk, I will discuss our work on engineering protein phase separation to generate designer membraneless organelles for synthetic biology applications. We devised strategies for enzymatically triggering assembly and disassembly of membraneless organelles, as well as approaches for recruiting specific cargo proteins into the synthetic organelles in living cells. Together, this work advances our knowledge of the sequence-to-phase behavior relationship of IDPs, important both for understanding the biochemistry of membraneless organelles, as well as for designing biomaterials and synthetic organelles.
~ Coffee/tea will be served prior to lecture~
Hosted by Professor Sagar Khare