Aaron Whiteley, Ph.D.

Research

I will investigate how a family of inflammatory proteins called NOD-like receptors (NLRs) establish the first line of defense against viral infection in organisms as diverse as bacteria and humans. Bacteria, like animals, are constantly infected by viruses and are a model organism for understanding the immune system. In our own bodies, NLRs form the core of the inflammasome, an immune signaling complex that senses a variety of infections and rapidly initiates an inflammatory response. In my lab, I made the surprising discovery that NLRs are also present in bacteria, where they provide protection against the viruses that infect microbes. Because these inflammatory proteins are so structurally and functionally similar in bacteria and humans, I will use bacterial NLRs as a model system to explore the molecular mechanisms by which the human inflammasome allows us to recognize and clear infections. Using an array of methods in bioinformatics, microbial genetics, immunology, and virology, I will introduce mutations that lead to rare inflammatory disorders in humans into bacterial NLRs to determine whether these mutations activate NLRs in the absence of any infection, identify the “viral signatures” recognized by bacterial NLRs, and explore how human NLRs of unknown function also act to defend cells against viral attack. My findings will unlock NLRs as therapeutic targets that can be activated to treat viral infections and boost immune responses to vaccines.