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Seminar: ​Programming Liquid-Liquid Phase SeparationÌýof Intrinsically Disordered Protein-Nucleic Acid Polymer Solutions

Speaker: Nick J. Carroll, assistant professor of chemical and biological engineering, University of New MexicoÌý

Host: Wyatt Shields

Seminar Abstract
Aqueous multi-phase systems comprising immiscible biopolymer solutions are ubiquitous in biological cells. However, the structure-to-function relationship and the physics describing the behavior of these polymer systems are, in general, not well understood. For example, almost all proteins have a specific three-dimensional structure that maintains its specific activity in the cell. One class of phase separating proteins, which has flown under the radar for decades, do not. They are referred to as intrinsically disordered proteins (IDPs). Their role in the cell appears to be to spontaneously associate with other proteins and nucleic acids in phase separated compartments called ‘membraneless organelles’ to activate them collectively. This is an important function to include in the design of a synthetic cell and for integration with cellular regulatory systems.

Our work explores how we can leverage polymer physics combined with the blueprint provided by the cell to engineer synthetic membraneless organelles comprising phase separated protein/DNA/RNA components in microdroplets. Our experimental results characterizing the morphology and composition of these liquids are interpreted by simple mean field Flory-Huggins equilibrium thermodynamics combined with formalisms describing the dynamics of phase separation via Cahn-Hilliard and Lattice Boltzmann theories. Potential broader impacts of this work include understanding how these interactions affect the regulation of gene expression and cell metabolism, understanding how dysfunctional interactions are linked to neurodegenerative disorders, and the design of synthetic cellular systems to create membraneless organelles to control a variety of biological processes at the molecular level.

Biosketch
Nick Carroll received his BS and PhDÌýin chemical engineering from the University of New Mexico. After his postdoctoral research at Harvard (applied physics) and Duke (biomedical engineering) universities, he took a position as an assistant professor of chemical and biological engineering at UNM in 2016. His research mainly focuses on liquid phase separation of intrinsically disordered proteins that bind nucleic acids to create condensed phase assemblies that recapitulate the structure and environmental responsiveness of membraneless organelles in living cells. In 2021, he received the NSF CAREER award, was selected as part of the 2021 Class of Influential Researchers by the American Chemical Society journal, Industrial & Engineering Chemistry Research (I&EC). Carroll has received $3.2 millionÌýin research dollars from NSF and DOE funding agencies.