Abstract:
A third of eukaryotic proteins contain long disordered regions with fluctuating structures that defy the sequence-structure-function paradigm. This prevalence of the disorder and the fact that it is often evolutionarily conserved have suggested critical functional roles. But what are these roles? Recent experiments are finding the ubiquitous presence of mesoscopic membraneless bodies in cells that form via liquid-liquid phase-separation of protein and nucleic acid mixtures. The proteins in these assemblies are frequently highly disordered, with low complexity sequences. Mutagenesis studies show that point mutations in disordered regions can often act as functional switches for various proteins, including enzymes, ion changes, and transcription factors. Disentangling the roles of sequence-specific interactions and environmental conditions on dynamics and phase separation of disordered biomolecules poses significant challenges for theory and experiment. Our group employs multi-scale computational techniques to uncover functional mechanisms of disorder in sensing, adaptation, and self-assembly of biomolecules. I will present our recent findings on disorder-mediated thermal adaptation, protein-RNA phase transitions, and mesoscale modeling chromatin organization during the talk.
