Our 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. We 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.
We study the molecular mechanisms of signal transduction by theTLRs using the methods of biophysics, structural biology, single molecule imaging, molecular genetics and cell biology.
Lab members: Farhana Ahmadi, Alkisti Alveropoulou-Malli, Istvan Foldi, Jukka Aurikko, Anthony Dossang, Monique Gangloff, Miranda Lewis, Ardi Liaunardy-Jopeace, Kristen E Mengwasser, Martin Moncrieffe, Ben Murton, Gugu Motshwene, Rui Wang, Olaniyi Opaleye, Brett Verstak, Samer Halibi.
1. Gay N & Gangloff M (2007) Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76:141-165.
2. Gay NJ, Gangloff M, & O'Neill LA (2011) What the Myddosome structure tells us about the initiation of innate immunity. Trends Immunol 32:104-109
3. Valkov E, et al. (2011) Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection. Proc Natl Acad Sci (USA), 108: 14879-84.