Sequence determinants of membraneless organelle rheology -- Research supplement to promote diversity

项目总结/文摘

PROJECT SUMMARY/ABSTRACT This is an application for a Research Supplement to Promote Diversity in Health-Related Research to complement our parent grant, “Sequence determinants of membraneless organelle rheology” (R35 GM142903). The supplement funds will support Bruna Favetta, who in Fall 2021 is starting her second year as a Ph.D. student in the Department of Biomedical Engineering at Rutgers University. Bruna has excellent background, motivation, and ability to contribute to the overall goals of the parent grant. The objective of the parent grant is to understand how the sequences of intrinsically disordered proteins (IDPs) contribute to the rheology of membraneless organelles (also known as biomolecular condensates), and ultimately how that rheology relates to function. Bruna is Hispanic and is committed to serving as a role model for underrepresented minorities in biomedical research, both at Rutgers and in her future research career. Bruna has conducted research at several universities and institutions beginning when she was only in high school, giving her a unique perspective on research in diverse settings around the globe. Bruna brings these experiences to advance her own research at Rutgers and to enrich the overall scientific community through fostering greater understanding of diversity in research. Together, we have crafted a plan for Bruna’s training and research during her Ph.D. studies. Bruna will study the rheology of biomolecular condensates formed from the IDPs of the SARS-CoV-2 virus. These proteins phase separate into biomolecular condensates during the viral replication lifecycle, and we hypothesize that the rheology of these condensates has important functional consequences for viral assembly, including membrane scission. The first goal is to quantify the rheology of the multiphasic condensates composed of the nucleocapsid (N) and membrane (M) proteins of SARS-CoV-2. Next, we will assess how perturbations to the rheology of these viral condensates may affect their biological function, such as orchestrating the important processes of membrane bending and viral membrane scission. Overall, this research will foster Bruna’s training and will advance our understanding of how IDP sequence determines biomolecular condensate rheology and how this rheology gives rise to biological function, which is the overarching focus of the parent R35 grant.