Grant: Operating Grant

Natural Killer (NK) cells are a critical arm of the host antiviral response in humans and mice alike. Our laboratory and others have previously shown that key mechanisms of NK cell function can be discovered using mouse genetic models of virus infection, even without the prior knowledge of their existence, location, and function. For example, this approach has provided a fresh view on how NK cells recognize and eliminate virally-infected cells. Here we propose to build on this productive strategy by exploiting mouse models of experimental infections relevant to human disease, new genetic resources unique to our laboratory, and the latest advances in genome research to identify genes that control the NK response against virus infections. A major focus will be to understand the mode of action and mechanisms regulated by the identified genes, as a means to open new avenues in our search for strategies to harness the NK cell antiviral activity in the clinic.