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Engineering Virus-Receptor Interactions to Determine their Roles in Cell Infection and Disease
Dr. Colin R. Parrish
Abstract
DESCRIPTION (provided by applicant): This proposal seeks support for a combined project to examine the interactions between viruses or viral proteins and their receptors on the surface of cells, with the object of determining how the affinity of the interaction or the specific contacts involved determine cell binding and infection. We will use various approaches of protein engineering and protein-protein binding studies to examine the interactions of the canine parvovirus capsid with the canine and feline transferrin receptors, and of the Hendra virus surface glycoprotein with the ephrin-B2 receptor on cells. Other models would use the parainfluenza virus type-3 (P13) to test its binding to sialic acids found on the surface of cells. Variants of each protein receptor that have higher or lower affinity than normal will be generated by rational design as well as directed evolution implemented by screening receptor libraries expressed in a yeast system.
This project will solidify some existing connections between the different laboratories, and we expect that this would lead to finding from the NIH for the Moscona, Porotto and Jin laboratories in the areas of paramyxovirus-receptor interactions leading to infection, and in the important biophysical properties of virus-receptor interactions (Jin laboratory). Existing connections between the laboratories include a former graduate student (Laura Palermo) from Colin Parrish's laboratory who is now doing a postdoctoral fellowship in Anne Moscona's laboratory. Moonsoo Jin is a new hire in the department of Biomedical Engineering, but is currently housed in the Baker Institute for Animal Health, the same building as the Parrish laboratory and so there are frequent informal and experimental contacts between those two laboratories. A former high school researcher in the Moscona laboratory (Olivia Diamond) is now a freshman at Cornell and she will be starting to work on this project in the spring of 2007, spending school terms in the Parrish lab and vacations and summers in the Moscona laboratory.
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