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Department of Veterinary Medicine

Cambridge Veterinary School

Studying at Cambridge

 

Dr Andrew Grant

Dr Andrew Grant

Senior Lecturer in Bacterial Pathogenesis

Andrew Grant is interested in taking PhD students.

Andrew Grant is available for consultancy.


Office Phone: +44 (0)1223 765801

Subject groups/Research projects

Infection and Immunity:
Mathematical Biology:

Departments and Institutes

Cambridge Infectious Diseases:

Research Interests

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 (C. jejuni and S. enterica) and host immune cells during infection
  2. Develop an appreciation of the genetic basis (and protein expression) of in vivo S. enterica adaptation and fitness during infection
  3. Determine the relative fitness of S. enterica mutants in gene targeted immunodeficient mice representative of human conditions known to predispose to salmonellosis
  4. Generation of live attenuated Salmonella vaccine strains.
  5. Study the factors involved in determining the shape of Campylobacter and how it is connected with virulence

Keywords

  • Bacteriology
  • Drug discovery and vaccinology
  • Resistance and immunity and infection
  • Epidemiology

Key Publications

 

  • Kaiser P, Regoes R, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt W-D. (2014) Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment. PLoS Biol. 12(2):e1001793
  • Mastroeni P and Grant A.(2013)  Dynamics of spread of Salmonella enterica in the systemic compartment. Microbes. Infect. 15, 849-857
  • Kaiser P, Slack E, Grant AJ, Hardt W-D, Regoes RR. (2013) Lymph node colonization dynamics after ortall Salmonella Typhimurium infection in mice. PLoS Pathog. 9(9):e1003532.
  • Restif O, Goh YS, Palayret M, Grant AJ, McKinley TJ, Clark MR, Mastroeni P. Quantification of the effects of antibodies on the extra-and intracellular dynamics of Salmonella enterica. (2012) J. R. Soc. Interface. 10(79):20120866
  • Grant AJ*, Morgan FLE, McKInley TJ, Foster GL, Maskell DJ, Mastroeni P. (2012) Attenuated Salmonella Typhimurium lacking the pathogenicity island-2 type 3 secretion system grow to high bacterial numbers inside phagocytes in mice. PLoS Pathog. 8(12): e1003070  (*Corresponding author)[
  • Periaswamy B, Maier L, Vishwakama V, Slack E, Kramer M, Andrews-Polymenis HL, McClelland M, Grant AJ, Suar M, Hardt W-D. (2012) Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice. PLoS One. 7(9):e45433
  • Holt JP, Grant AJ, Coward C, Maskell DJ, Quinlan JJ. (2012) Cj1051c is a Major Determinant for the Restriction Barrier of C. jejuni Strain NCTC11168. Appl. Environ. Microbiol. 78, 7841-7848
  • Staniewicz L, Donald A, Stokes D, Thomson N, Sivaniah E, Grant AJ, Bulmer D, Khan CM. (2012) The application of STEM an in-situ controlled dehydration of bacterial systems using ESEM. J. Microsc. Scanning. 34, 237-246
  • Bulmer DM, Kharraz L, Grant AJ, Dean P, Morgan FJ, Karavolos MH, Doble AC, McGhie EJ, Koronakis V, Daniel RA, Mastroeni P, Khan CM. (2012) The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella. PLoS Pathog. 8(1):e1002500[PubMed].
  • Chaudhuri RR, Yu L, Kanji A, Perkins TT, Gardner PP, Choudhary J, Maskell DJ, Grant AJ.* (2011) Quantitative RNA-seq analysis of the transcriptome of Campylobacter jejuni. Microbiol. 157, 2922-2932 (*Corresponding author)[PubMed].
  • Jansen AM, Hall LJ, Clare S, Goulding D, Holt K, Grant AJ, Mastroeni P, Dougan G, Robert A. Kingsley RA. (2011) A Salmonella Typhimurium-Typhi genomic chimera: A model to study Vi polysaccharide capsule function in vivo. PLoS Pathog. 7(7):e1002131[PubMed].
  • 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. 79, 2481-2488
  • 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. (*Corresponding author) [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.  (#Corresponding author)[ [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. (*Corresponding author) [[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]
  • Coward C, van Diemen PM, Conlan AJK, Grant AJ, Stevens MP, Gog JR, Jones MA, Maskell DJ. (2007) Competition between isogenic Campylobacter strains results in unpredictable population structures. Zoonoses Public Hlth. 54, 117-117
  • 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.  (#Corresponding author)[ [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)  (*Corresponding author)[
  • 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)  (#Corresponding author)
  • 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]
  • Farris M, Grant A, Jane S, Chad J, O'Connor CD. (1998) BipA affects Ca++ fluxes and phosphorylation of the translocated intimin receptor (Tir/Hp90) in host epithelial cells infected with enteropathogenic E. coli. Biochem. Soc. Trans. 26, S225
  • Farris M, Grant A, Richardson TB, O'Connoer CD. (1998) BipA: a tyrosine-phosphorylated GTPase that mediates interactions between enteropathogenic Escherichia coli (EPEC) and epithelial cells. Mol. Microbiol. 28, 265-279