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Identification of host-factors involved in the replication of SARS-CoV-2 and Influenza A using CRISPR/Cas9

The recent SARS-CoV-2 pandemic has demonstrated the susceptibility of human populations to the rapid spread of novel viral pathogens and the incredible effect they can have on our society. In order to prepare for the next potential outbreak and identify novel targets for the development of therapeutics a better understanding of the viral life cycle and the role of host-factors play at different stages is required. Currently, CRISPR/Cas9 based functional genetic screens have primarily identified host-proteins that function in early stages of viral infection. Our group is interested in developing new methods and techniques to leverage CRISPR/Cas9 for identification of host-factors in all stages of the viral life cycle, specifically for SARS-CoV-2 and Influenza A, thus providing new targets for therapeutics and a better understanding of human biology.

Creation of Novel CRISPR libraries

The goal of this work is to create and make available cutting-edge large scale CRISPR/Cas9 functional genomic resources for use by research communities. Human and mouse system researchers have successfully completed a large number of functional genomic screens, many of which have made high impact transformative discoveries. Such approaches are not possible in all other model systems because of the lack of the appropriate tools. The creation of these functional genomic resources will fulfill an unmet need thereby accelerating the discoveries made using important model systems

Role of dependency factors in HBV infection

Chronic HBV infection is an etiological agent for cirrhosis and hepatocellular carcinoma (HCC) and leads to approximately 900,000 deaths per year due to infection related health complications. Recently, our group identified a number of poorly understood host proteins including the zinc-finger protein ZCCHC14 whose depletion resulted in reduction of HBV infection. Currently the role of ZCCHC14 in HBV infection and human biology is poorly understood. The McDougall Lab is focused on identification of novel protein-protein interactions and protein nucleic acid interactions of ZCCHC14.