Student: Roshan Mammen Regy
Project: Sequence Dependent Phase Separation of Protein - Polynucleotide Mixtures Elucidated Using Molecular Simulations
View: Research Poster (PDF) | Presentation (YouTube)
Department: Chemical and Biomolecular Engineering
Advisor: Jeetain Mittal
Abstract
Ribonucleoprotein (RNP) granules are membraneless organelles (MLOs), which majorly consist of RNA and RNA-binding proteins and are formed via liquid–liquid phase separation (LLPS). Experimental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (IDPs) and nucleic acids like RNA and other polynucleotides play a key role in modulating protein phase separation. There is currently a dearth of modelling techniques which allow one to delve deeper into how polynucleotides play the role of a modulator/promoter of LLPS in cells using computational methods. Here, we present a coarse-grained polynucleotide model developed to fill this gap, which together with our recently developed HPS model for protein LLPS, allows us to capture the factors driving protein-polynucleotide phase separation. We explore the capabilities of the modelling framework with the LAF-1 RGG system which has been well studied in experiments and also with the HPS model previously. Further taking advantage of the fact that the HPS model maintains sequence specificity we explore the role of charge patterning on controlling polynucleotide incorporation into condensates. With increased charge patterning we observe formation of structured or patterned condensates which suggests the possible roles of polynucleotides in not only shifting the phase boundaries but also introducing microscopic organization in MLOs.
About Roshan Mammen Regy
Roshan Mammen Regy is a Ph.D student advised by Professor Jeetain Mittal at the Chemical and Biomolecular Engineering Department, Lehigh University. His work focuses on investigating sequence- specific phase separation of intrinsically disordered proteins using computational methods. He started his Ph.D. in Chemical Engineer- ing at Lehigh University in 2018 after finishing his undergraduate studies in Chemical Engineering in 2017 from B.I.T.S. Pilani, India.