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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at The University of Cambridge

Studying at Cambridge

 

Dr Andrew James Grant

Dr Andrew James Grant

-Senior Lecturer in Bacterial Pathogenesis

Research group studies host-pathogen interactions and the molecular basis of virulence

Andrew Grant is accepting applications for PhD students.

Andrew Grant is available for consultancy.

Department of Veterinary medicine
University of Cambridge
Madingley Road

Cambridge , Cambridgeshire CB3 0ES
Office Phone: 01223 765801

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 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.

Keywords

  • Genomics
  • Pathogen Evolution
  • Genetics
  • Vaccine development
  • Molecular Biology
  • Global Health
  • Gene Expression
  • Antimicrobial resistance
  • Africa
  • Infection
  • Sequencing
  • Host-Pathogen Interaction
  • Virulence
  • Transcriptomics
  • Vaccine
  • Bacteriology
  • Immunology
  • Dynamics
  • Antibody
  • Gene Regulation

Topics

  • Genomics
  • Campylobacteriosis
  • Typhoid Fever
  • Salmonellosis
  • Public Health
  • Campylobacter
  • Zoonoses
  • Gastroenteritis
  • Salmonella
  • Escherichia coli

Key Publications

§  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

§  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 DW, Thompson AJ, Corletto F, Reckless J, Loke JCT, Lapaque N, Grant AJ, Mastroeni P, Grainger DJ, Padgett CL, O’Brien JA, Miller NGA, Trowsdale J, Lummis SCR, Menon DK, Beech JS. (2011) Anaesthetic impairment of immune function is mediated via GABAA receptors. PLoS One. 6, e17152

§  Goh YS, Grant AJ, Restif O, McKinley TJ, Armour KL, Clark MR, Mastroeni P. (2011) Human IgG isotypes and activating Fcgamma receptors in the interaction of S. Typhimurium with phagocytic cells. Immunol. 133, 74-83

§  Mastroeni P, Morgan FJ, McKinley TJ, Shawcroft E, Clare S, Maskell DJ, Grant AJ#. (2011) Enhanced virulence of Salmonella enterica serovar Typhimurium after passage through mice. Infect. Immun. 79, 636-643. (#Corresponding author)

§  Osman D, Waldron KJ, Denton H, Taylor CM, Grant AJ, Mastroeni P, Robinson NJ, Cavet JS. (2010) Copper homeostasis in salmonella is atypical and copper-CueP is a major periplasmic metal complex. J. Biol. Chem. 285, 25259-25268.

§  Javed MA, Grant AJ, Bagnall MC, Maskell DJ, Newell DG, Manning G. (2010) Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion. Microbiol. 156, 1134-1143.

§  Buckley AM, Wang J, Hudson DL, Grant AJ, Jones MA, Maskell DJ, Stevens MP. (2010) Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry. Vaccine. 28, 1094-1105

§  Grant AJ*#, Foster GL*, McKinley TJ, Brown SP, Clare S, Maskell DJ, Mastroeni P. (2009) Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections. Infect. Immun. 77, 5608-5611 (*Joint first authorship, (#Corresponding author))

§  Wright JA, Grant AJ, Hurd D, Harrison M, Guccione E, Kelly DJ, Maskell DJ. (2009) Metabolite and transcriptome analysis of Campylobacter jejuni in vitro growth dynamics reveals a stationary phase physiological switch. Microbiol. 155, 80-94

§  Mastroeni P*, Grant AJ*, Restif O, Maskell DJ. (2009) Salmonella enterica depends on a complex "hit-and-run" strategy for growth and spread in systemic organs. Nat. Rev. Microbiol. 7, 73-80 (*Joint first authorship)

§  Grant AJ, Restif O, McKinley TJ, Sheppard M, Maskell DJ, and Mastroeni P. (2008) Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLoS Biol. 6, e74

§  Grant AJ, Sheppard M, Deardon R, Brown S, Foster G, Bryant C, Maskell DJ and Mastroeni P. (2008) Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice. Immunol. 125, 28-37

§  Foster GL, Barr TA, Grant AJ, McKinley TJ, Bryant CE, MacDonald A, Gray D, Yamamoto M, Akira S, Maskell DJ and Mastroeni P. (2008) Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated Salmonella enterica vaccine via TLR4-dependent IL-10 production with the involvement of both TRIF and MyD88. Immunol. 124, 469-479

§  Conlan AJK, Coward C, Grant AJ, Maskell DJ and Gog J. (2007) Campylobacter jejuni colonisation and transmission in broiler chickens: A modelling perspective. J. R. Soc. Interface, 4, 819-829

§  Beech JS, Wheeler DW, Reckless J, Grant AJ, Price J, Mastroeni P, Grainger DJ and Menon DK. (2007) The MHP36 line of murine neural stem cells express functional CXCR1 chemokine receptors that initiate chemotaxis in vitroJ. Neuroimmunol. 184, 198-208

§  Brown SP, Cornell SJ, Sheppard M, Grant AJ, Maskell DJ, Grenfell BT and Mastroeni P. (2006) Intracellular demography and the dynamics of Salmonella typhimurium infection. PLoS Biol. 4, 2091-2098

§  Grant AJ, Woodward J and Maskell DJ. (2006) Development of an ex vivo organ culture model using human and porcine gastro-intestinal tissue and Campylobacter jejuni. FEMS Microbiol. Lett. 263, 240-243

§  Coward C*, Grant AJ*, Swift C, Philp J, Towler R, Heydarian M, Frost J and Maskell DJ. (2006) Phase-variable surface structures are required for infection of Campylobacter jejuni by bacteriophages. Appl. Environ. Microbiol. 72, 4638-4647 (*Joint first authorship)

§  Grant AJ*, Coward C*, Jones MA, Woodall CA, Barrow PA and Maskell DJ. (2005) Signature tagged transposon mutagenesis studies demonstrate the dynamic nature of caecal colonisation of two-week-old chickens by Campylobacter jejuni. Appl. Environ. Microbiol. 71, 8031-8041 (*Joint first authorship)

§  Grant AJ, Farris M, Alefounder P, Williams PH, Woodward MJ, O'Connor CD. (2003) Co-ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic Escherichia coli (EPEC). Mol. Microbiol. 48, 507-521

§  Grant AJ, Haigh R, Williams P, O'Connor CD. (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, 145-151

§  Owens RM, Grant A, Davies N, O'Connor CD. (2001) Copurification of the Lac repressor with polyhistidine-tagged proteins in immobilized metal affinity chromatography. Protein Expr Purif. 21, 352-360

§  Farris M, Grant A, Jane S, Chad J, O'Connor CD. 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. 1998 Aug;26(3):S225

§  Farris M, Grant A, Richardson TB, O'Connor CD. BipA: a tyrosine-phosphorylated GTPase that mediates interactions between enteropathogenic Escherichia coli (EPEC) and epithelial cells. Mol Microbiol. 1998 Apr;28(2):265-79