Department of Veterinary Medicine

Research in Veterinary Medicine

Other relevant links

• http://www.infectiousdisease.cam.ac.uk/directory/a-z.php

Research description

We study Pattern Recognition Receptors (PRRs), such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs), in different mammalian species investigating their roles in responding to both purified bacterial ligands and infection with Salmonella entericia serovar Typhimurium (in collaboration with Duncan Maskell). We use use chimeric receptor constructs to study species-specific ligand interaction at the TLR4/MD2 complex (in collaboration with Nick Gay, Biochemistry). We are using single molecule florescence techniques to study how type I receptors such as TLR4 forms active complexes and to studying the recruitment of adaptor proteins to TLR4 (in collaboration with David Klenerman, Chemistry). We are also studying which PRRs detect S. Typhimurium to drive an adaptive immune responses focussing on the inflammasome. We work with Pietro Cicuta (Physics), Julia Gog (DAMPT) and Ray Goldstein (DAMPT) to study bacterial interactions with cells and respiratory tissues using mathematical modelling, optical tweezers and real-time imaging.

Our work is funded by the Wellcome Trust, the MRC, the BBSRC and the HBLB.

Main collaborators

• Pietro Cicuta, Department of Physics, Cambridge
• Nick Gay, Department of Biochemistry, Cambridge
• Julia Gog, DAMTP, Cambridge
• Ray Goldstein, DAMPT, Cambridge
• Duncan Maskell, Department of Veterinary Medicine, Cambridge
• David Spring, Department of Chemistry, Cambridge
• David Klenerman, Department of Chemistry, Cambridge
• Kate Fitzgerald, UMass Medical School, Worcester, USA
• Doug Golenbock, UMass Medical School, Worcester, USA
• Jay Hinton, IFR, Norwich
• Luke O'Neill, Trinity College, Dublin, Ireland
• Michael White, University of Liverpool

Key publications since 2007

• Bryant, C. E., D. R. Spring, M. Gangloff and N. J. Gay "The molecular basis of the host response to lipopolysaccharide." Nat Rev Microbiol 8(1): 8-14. [PubMed]
• Bryant, C. and K. A. Fitzgerald (2009). "Molecular mechanisms involved in inflammasome activation." Trends Cell Biol 19(9): 455-64. [PubMed]
• Talbot, S., S. Totemeyer, M. Yamamoto, S. Akira, K. Hughes, D. Gray, T. Barr, P. Mastroeni, D. J. Maskell and C. E. Bryant (2009). "Toll-like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar typhimurium infection, but not for the initiation of bacterial clearance." Immunology 128(4): 472-83. [PubMed]
• Wright, J. A., S. S. Totemeyer, I. Hautefort, C. Appia-Ayme, M. Alston, V. Danino, G. K. Paterson, P. Mastroeni, N. Menager, M. Rolfe, A. Thompson, S. Ugrinovic, L. Sait, T. Humphrey, H. Northen, S. E. Peters, D. J. Maskell, J. C. Hinton and C. E. Bryant (2009). "Multiple redundant stress resistance mechanisms are induced in Salmonella enterica serovar Typhimurium in response to alteration of the intracellular environment via TLR4 signalling." Microbiology 155(Pt 9): 2919-29. [PubMed]
• Walsh, C., M. Gangloff, T. Monie, T. Smyth, B. Wei, T. J. McKinley, D. Maskell, N. Gay and C. Bryant (2008). "Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa." J Immunol 181(2): 1245-54. [PubMed]