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Daryll Vanover
PhD Proposal Presentation
Date: September 27th, 2017
Time: 9:00am
Location: Engineered Biosystems Building (EBB) CHOA Seminar Room
Advisor: Dr. Philip J. Santangelo
Thesis Committee:
Dr. Elizabeth Wright
Dr. Brandon Dixon
Dr. Krishnendu Roy
Dr. Peng Xi
Title: Molecular toolbox for characterizing, preventing, and treating human respiratory syncytial virus infections
Abstract:
Respiratory syncytial virus (RSV) remains the leading cause of acute lower respiratory infections worldwide in young children due to the lack of an effective vaccine. In this work, we will investigate two approaches towards the long-term mitigation and prevention of RSV infections: 1) improve on our fundamental understanding of RSV virion assembly via the further development of live cell compatible imaging tools for both RSV glycoproteins and genomic RNA as a means of identifying new drug targets, and 2) develop RNA-based therapeutics against the RSV F protein. Towards improving our understanding of RSV assembly, we will develop fluorophore-conjugated lectins to selectively label the RSV glycoprotein (RSV G) in live cells during an infection. Using these probes in conjunction with RNA imaging probes, we will investigate G protein and genomic RNA localization and dynamics during viral filament assembly. Specifically, we will interrogate the role of the secretory membrane system and the cytoskeleton in this process. In addition, to improve our understanding of G protein localization at much higher resolution, we will develop gold-conjugated probes for the G to enable electron microscopy compatibility. Towards the development of RNA-based therapeutics for RSV, mRNA based constructs will be developed to promote RSV infection mitigation and they will be tested in a mouse model of RSV infection.
