Department of Veterinary Medicine

Research in Veterinary Medicine

Other relevant links

• http://www.infectiousdisease.cam.ac.uk/

Research description

My research interests lie in host-pathogen interactions and the molecular basis of virulence. My research is broad-ranging and multidisciplinary, from understanding the roles of individual bacterial proteins in virulence, studying the within-host population dynamics of bacterial pathogens and understanding the host response to infection. My research focuses on bacterial pathogens of veterinary and clinical significance, including; enteropathogenic Escherichia coli (EPEC), Campylobacter jejuni and Salmonella enterica. I aim to use integrated approaches where advanced molecular, genomic, proteomic and microscopy techniques, in combination with mathematical and statistical models, enable me to tease out heterogeneous events in infection. My recent work has concentrated on a systems-level in vivo analysis of Salmonella-host interactions, to provide the mechanistic detail to describe infective disease within the host.

Current research projects aim to:

1. Develop an understanding of the interactions between individual bacterial populations and host immune cells during infection
2. Develop an appreciation of the genetic basis of in vivo bacterial adaptation and fitness during infection
3. Determine the identity and function of C. jejuni proteins involved in both host cell attachment, and invasion and modulation of host cell function
4. Study the factors involved in determining the shape of Campylobacter and how it is connected with virulence.

Main collaborators

• Dr Pietro Mastroeni, University of Cambridge
• Professor Duncan Maskell, University of Cambridge
• Dr Olivier Restif, University of Cambridge
• Professor Athene Donald, University of Cambridge
• Professor Gordon Dougan, Wellcome Trust Sanger Institute
• Professor Julian Parkhill, Wellcome Trust Sanger Institute
• Dr Nick Thomson, Wellcome Trust Sanger Institute
• Dr Jyoti Choudhary, Wellcome Trust Sanger Institute
• Professor Tom Humphrey, University of Liverpool
• Dr Anjam Khan, University of Newcastle

Key publications since 2001

• Mastroeni P, Grant AJ. (2011) The spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants. Exp. Rev. Mol. Med. 13, e12 [PubMed].
• Janis C, Grant AJ, McKinley TJ, Morgan FJE, John VF, Houghton J, Kingsley RA, Dougan G, Mastroeni P. (2011) In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo inducible promoter. Infect. Immun. Mar 14 [Epub ahead of print]
• Wheeler, D. W., A. J. Thompson, F. Corletto, J. Reckless, J. C. Loke, N. Lapaque, A.J. Grant, P. Mastroeni, D. J. Grainger, C. L. Padgett, J. A. O'Brien, N. G. Miller, J. Trowsdale, S. C. Lummis, D. K. Menon and J. S. Beech Anaesthetic Impairment of Immune Function Is Mediated via GABA(A) Receptors. PLoS One 6(2): e17152. [PubMed]
• Goh, Y. S., A.J. Grant, O. Restif, T. J. McKinley, K. L. Armour, M. R. Clark and P. Mastroeni Human IgG isotypes and activating Fcgamma receptors in the interaction of Salmonella enterica serovar Typhimurium with phagocytic cells. Immunology 133(1): 74-83. [PubMed]
• Mastroeni, P., F. J. Morgan, T. J. McKinley, E. Shawcroft, S. Clare, D. J. Maskell and A. J. Grant Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice. Infect Immun 79(2): 636-43. [PubMed]
• Osman, D., K. J. Waldron, H. Denton, C. M. Taylor, A. J. Grant, P. Mastroeni, N. J. Robinson and J. S. Cavet Copper homeostasis in Salmonella is atypical and copper-CueP is a major periplasmic metal complex. J Biol Chem 285(33): 25259-68. [PubMed]
• Javed, M. A., A. J. Grant, M. C. Bagnall, D. J. Maskell, D. G. Newell and G. Manning Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion. Microbiology 156(Pt 4): 1134-43. [PubMed]
• Buckley, A. M., J. Wang, D. L. Hudson, A. J. Grant, M. A. Jones, D. J. Maskell and M. P. Stevens Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry. Vaccine 28(4): 1094-105. [PubMed]
• Grant, A. J.**, G. L. Foster*, T. J. McKinley, S. P. Brown, S. Clare, D. J. Maskell and P. Mastroeni (2009). Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections. Infect Immun 77(12): 5608-11. [PubMed] (*Joint first authorship, *Corresponding author)
• Wright, J. A., A. J. Grant, D. Hurd, M. Harrison, E. J. Guccione, D. J. Kelly and D. J. Maskell (2009). Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth reveals a stationary-phase physiological switch. Microbiology 155(Pt 1): 80-94. [PubMed]
• Mastroeni, P*, A. Grant*, O. Restif and D. Maskell (2009). A dynamic view of the spread and intracellular distribution of Salmonella enterica. Nat Rev Microbiol 7(1): 73-80. [PubMed] (*Joint first authorship)
• Grant, A. J., O. Restif, T. J. McKinley, M. Sheppard, D. J. Maskell and P. Mastroeni (2008). Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLoS Biol 6(4): e74. [PubMed]
• Grant, A. J., M. Sheppard, R. Deardon, S. P. Brown, G. Foster, C. E. Bryant, D. J. Maskell and P. Mastroeni (2008). Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice. Immunology 125(1): 28-37. [PubMed]
• Foster, G. L., T. A. Barr, A. J. Grant, T. J. McKinley, C. E. Bryant, A. MacDonald, D. Gray, M. Yamamoto, S. Akira, D. J. Maskell and P. Mastroeni (2008). Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated S. enterica vaccine via Toll-like receptor 4-dependent interleukin-10 production with the involvement of both TRIF and MyD88. Immunology 124(4): 469-79. [PubMed]
• Conlan, A. J., C. Coward, A. J. Grant, D. J. Maskell and J. R. Gog (2007). Campylobacter jejuni colonization and transmission in broiler chickens: a modelling perspective. J R Soc Interface 4(16): 819-29. [PubMed]
• Beech, J. S., D. W. Wheeler, J. Reckless, A. J. Grant, J. Price, P. Mastroeni, D. J. Grainger and D. K. Menon (2007). The MHP36 line of murine neural stem cells expresses functional CXCR1 chemokine receptors that initiate chemotaxis in vitro. J Neuroimmunol 184(1-2): 198-208. [PubMed]
• Brown, S. P., S. J. Cornell, M. Sheppard, A. J. Grant, D. J. Maskell, B. T. Grenfell and P. Mastroeni (2006). Intracellular demography and the dynamics of Salmonella enterica infections. PLoS Biol 4(11): e349. [PubMed]
• Grant, A. J., J. Woodward and D. J. Maskell (2006). Development of an ex vivo organ culture model using human gastro-intestinal tissue and Campylobacter jejuni. FEMS Microbiol Lett 263(2): 240-3. [PubMed]
• Coward, C.*, A. J. Grant*, C. Swift, J. Philp, R. Towler, M. Heydarian, J. A. Frost and D. J. Maskell (2006). Phase-variable surface structures are required for infection of Campylobacter jejuni by bacteriophages. Appl Environ Microbiol 72(7): 4638-47. [PubMed] (*Joint first authorship)
• Grant, A. J*., C. Coward*, M. A. Jones, C. A. Woodall, P. A. Barrow and D. J. Maskell (2005). Signature-tagged transposon mutagenesis studies demonstrate the dynamic nature of cecal colonization of 2-week-old chickens by Campylobacter jejuni. Appl Environ Microbiol 71(12): 8031-41. [PubMed] (*Joint first authorship)
• Grant, A. J., M. Farris, P. Alefounder, P. H. Williams, M. J. Woodward and C. D. O'Connor (2003). Co-ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic Escherichia coli (EPEC). Mol Microbiol 48(2): 507-21. [PubMed]
• Grant, A. J., R. Haigh, P. Williams and C. D. O'Connor (2001). An in vitro transposon system for highly regulated gene expression: construction of Escherichia coli strains with arabinose-dependent growth at low temperatures. Gene 280(1-2): 145-51. [PubMed]
• Owens, R. M., A. Grant, N. Davies and C. D. O'Connor (2001). Copurification of the Lac repressor with polyhistidine-tagged proteins in immobilized metal affinity chromatography. Protein Expr Purif 21(2): 352-60. [PubMed]