<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-7.xsd"><mods:titleInfo><mods:title>Biophysical studies of phase separation: RNA-binding proteins at the nexus of neurodegeneration, cancer and viral infection</mods:title></mods:titleInfo><mods:typeOfResource authority="primo">dissertations</mods:typeOfResource><mods:name type="personal"><mods:namePart>Perdikari, Theodora Myrto</mods:namePart><mods:role><mods:roleTerm type="text">creator</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Fawzi, Nicolas</mods:namePart><mods:role><mods:roleTerm type="text">Advisor</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Colvin, Vicki</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Tang, Jay</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Karniadakis, George</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Wheeler, Richard</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="corporate"><mods:namePart>Brown University. Biology and Medicine: Biomedical Engineering</mods:namePart><mods:role><mods:roleTerm type="text">sponsor</mods:roleTerm></mods:role></mods:name><mods:originInfo><mods:copyrightDate>2022</mods:copyrightDate></mods:originInfo><mods:physicalDescription><mods:extent>xix, 230 p.</mods:extent><mods:digitalOrigin>born digital</mods:digitalOrigin></mods:physicalDescription><mods:note type="thesis">Thesis (Ph. D.)--Brown University, 2022</mods:note><mods:genre authority="aat">theses</mods:genre><mods:abstract>Liquid-liquid phase separation (LLPS) is a prominent organizer of cellular biochemistry. Dozens of liquid-like condensates are found throughout the nucleus and the cytoplasm and the vast majority of them are enriched in RNA-binding proteins; the maestros of gene expression. Fused in Sarcoma (FUS) is an RNA-binding protein that phase separates via its low-complexity (LC) and arginine- glycine-glycine (RGG) domains. FUS localizes in liquid-like assemblies like stress granules and DNA- repair foci when the cell needs to combat stress and DNA damage respectively. However, mutations and/or abnormal levels of post-translational modifications (PTMs) disorient physiologically relevant interactions of FUS with RNA and other binding partners leading to a number of neurodegenerative diseases and cancers with unmet therapeutic needs. Combining computer simulations with solution- state nuclear magnetic resonance (NMR) has emerged as an unparalleled method to obtain atomic- level details of liquid-like structures. In this thesis, the main focus is towards a deeper understanding of the biophysical rules governing the interplay of FUS with PTMs, RNA and condensate-modifying molecules. In Chapter 2, I use coarse-grained (CG) modeling to show how measuring the effect of PTMs like phosphorylation and acetylation on the single-chain properties of various systems including FUS is predictive of their propensity to phase separate. In Chapter 3, I decipher the behavior of SARS-CoV-2 nucleocapsid protein which phase separates with RNA as I was equipped to face this challenge during the course of my doctoral studies in LLPS. In Chapter 4, I use NMR and biochemical assays to probe how condensate-modifying molecules alter FUS structure, phase behavior and interactions with RNA. In Chapter 5, I demonstrate that arginine-specific contacts are necessary for FUS RGG-RNA interactions and methylation alters heterotypic interactions of FUS RGG with RNA and the LC domain. Collectively, my work provides a detailed molecular view into the effect of PTMs, RNA and drug-like molecules on RNA-binding protein assembly. This knowledge can be harnessed to design in-vitro drug-design studies that screen the effect of drug molecules against FUS LLPS and aggregation.</mods:abstract><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01040325"><mods:topic>Nuclear magnetic resonance</mods:topic></mods:subject><mods:subject><mods:topic>liquid-liquid phase separation</mods:topic></mods:subject><mods:subject><mods:topic>Fused in Sarcoma</mods:topic></mods:subject><mods:subject><mods:topic>SARS-CoV-2</mods:topic></mods:subject><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01086260"><mods:topic>RNA-protein interactions</mods:topic></mods:subject><mods:subject><mods:topic>Biomolecular condensates</mods:topic></mods:subject><mods:subject><mods:topic>Molecular Dynamics Simulation</mods:topic></mods:subject><mods:language><mods:languageTerm authority="iso639-2b">English</mods:languageTerm></mods:language><mods:recordInfo><mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource><mods:recordCreationDate encoding="iso8601">20220706</mods:recordCreationDate></mods:recordInfo><mods:identifier type="doi">10.26300/7fnh-8877</mods:identifier></mods:mods>