Speaker: Dr. Kelsey Gasior, Univeristy of Ottawa
Title: Untangling Small-Molecule Interactions Driving Intracellular Phase Separation
Abstract: An emerging mechanism for intracellular organization is liquid-liquid phase separation (LLPS). Found in both the nucleus and the cytoplasm, liquidlike droplets condense to create compartments that are thought to localize factors, such as RNAs and proteins, and promote biochemical interactions. Many proteins interact with different RNA species to create droplets necessary for cellular functions, such as polarity and nuclear division. Further, the proteins that promote phase separation are frequently coupled to multiple RNA binding domains and multiple RNAs can interact with a single protein leading to a large number of potential multivalent interactions. In this work, we present a multiphase, diffuse interface mathematical model to examine the RNA-protein interactions driving LLPS. Using a ‘start simple, build up’ approach, we incorporate bivalent protein-RNA dynamics and RNA competition in the droplet field. Numerical simulations reveal spatiotemporal heterogeneity can emerge at both the intra-droplet and droplet field level with simple binding reactions and RNA competition for a shared resource, protein. Further, our approach is also applicable to other phase separated systems; our model predicted that protein anisomes associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which was then confirmed experimentally by our biological collaborators.
Friday 29 September 2023