Nick Gay's research group studies how microbial pathogens such as bacteria and viruses are recognized by the pattern recognition receptors (PRRs) of the innate immune system and the signaling responses that are generated. They are especially interested in the Toll-like receptors (TLRs). The microbial molecules or PAMPs that are recognized by TLRs can be divided broadly into two groups, microbial lipids such as lipopolysaccharide (LPS) and non-self nucleic acids from bacteria, viruses and other pathogenic microorganisms. These PAMPs bind and activate TLRs by promoting the dimerization of two receptor ectodomains and this in turn causes the cytosolic Toll/IL1 domains (TIR) to associate, creating a signal induced scaffold for the assembly of a postreceptor complex. TLRs function not only in immune system cells such as macrophages and dendritic cells but also at many other sites that require immune surveillance such intestinal mucosae and airway epithelia.

They study the molecular mechanisms of signal transduction by the TLRs using the methods of biophysics, structural biology, single molecule imaging, molecular genetics and cell biology.