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Department of Veterinary Medicine

Cambridge Veterinary School

I have been fortunate enough over the last 45 years, to work on many pioneering Bacterial Vaccine projects that have arisen from utilising basic but essential principles of Microbiology, Immunology and Pathogenicity while working with a wide range of colleagues and friends. These include, but not limited to William Turner (Staphylococcus aureus Leucocidin and Delta Toxin-Mastitis), Lazlo Nagy and Tom Mackensie (ETEC and piglet Vaccines, Gletvax), Gordon Dougan and Pavel Novotny (Whooping Cough-Pertactin), Neil Fairweather (Tetanus Fragment C) and Salmonella typhi attenuated vaccines (Steve Chatfield and Gordon Dougan-Wellcome Foundation, Beckenham in Kent and Medeva at Imperial College in London).

Salmonella typhi has proven a marvellous vehicle to study regulation of genes and with a focus on Vi capsule regulation. In 1996 we discovered that the OmpR-EnvZ two component regulator played a key role in controlling Vi capsule biosynthesis. Along the way, we have used Vi Bacteriophage in conjunction with TraDIS libraries to elucidate the various regulatory mechanisms that control the expression of the S. typhi Vi Capsule and discovered its probable master co-ordinator of all this, oxyR (in conjunction with oxyS). With that in mind, we have also examined how Salmonella typhi mutants survive under high Bile Salt concentrations that seem to defy what is understood to be the key role played by the Vi capsule in its survival in the Bile Duct. That underscored the complexity of gene regulation under such stress conditions.

Other projects I have undertaken include using bioinformatics to delve into the amazing range of Phage-Plasmids related to N15, pHCM2 and P1that exist in many enteric bacteria. It is likely that new ones that have been over-looked previously will come to light as high quality complete genomes with extra-cellular episomes are released onto databases.

Recently we have carried out, along with colleagues at the Monash in Melbourne, a complete analysis using CyroEM of the flagella targeting phage, YSD1, and RAD2 that uses the K2-type capsular polysaccharide of Klebsiella pneumonia as its receptor.

Other scientific interests beside my ongoing research include a fascination in Early Life on Earth and how it arose from 3.5 Billion years ago, through to the prokaryotes and unicellular Eucaryotes and onto Chanoflagellates, Sponges, the mass Oxidation Events and into the Burgess Shale history and the rise of Multi-cellularity. The microbiological-unicellular protozoa interactions that go back all this time in history was the nursery ground for all the pathological, mutualistic and symbiotic relationships we are all familiar with today in disease and the environment! A SGM Symposium I helped organised in 2015 focused on all these topics and also included Talks on Giant Viruses, the Archaea and their Viruses, Legionella pnemoniae and its interactions with amoeba.

My other interests are quite varied and include Classical Music Concerts, Old Radios, Astronomy, Films, Photography, Cave paintings, Art in General and 19th  century American Landscape paintings and Byzantine Art/history in particular!

Publications that highlight my Research Interests:-

The flagellotropic bacteriophage YSD1 targets Salmonella Typhi with a Chi-like protein tail fibre.

Dunstan RA, Pickard D, Dougan S, Goulding D, Cormie C, Hardy J, Li F, Grinter R, Harcourt K, Yu L, Song J, Schreiber F, Choudhary J, Clare S, Coulibaly F, Strugnell RA, Dougan G, Lithgow T. Mol Microbiol. 2019 Dec;112(6):1831-1846. doi: 10.1111/mmi.14396. Epub 2019 Oct 9. PMID: 31556164

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, Kingsley RA, Thomson NR, Keane JA, Weill FX, Edwards DJ, Hawkey J, Harris SR, Mather AE, Cain AK, Hadfield J, Hart PJ, Thieu NT, Klemm EJ, Glinos DA, Breiman RF, Watson CH, Kariuki S, Gordon MA, Heyderman RS, Okoro C, Jacobs J, Lunguya O, Edmunds WJ, Msefula C, Chabalgoity JA, Kama M, Jenkins K, Dutta S, Marks F, Campos J, Thompson C, Obaro S, MacLennan CA, Dolecek C, Keddy KH, Smith AM, Parry CM, Karkey A, Mulholland EK, Campbell JI, Dongol S, Basnyat B, Dufour M, Bandaranayake D, Naseri TT, Singh SP, Hatta M, Newton P, Onsare RS, Isaia L, Dance D, Davong V, Thwaites G, Wijedoru L, Crump JA, De Pinna E, Nair S, Nilles EJ, Thanh DP, Turner P, Soeng S, Valcanis M, Powling J, Dimovski K, Hogg G, Farrar J, Holt

A Genomewide Mutagenesis Screen Identifies Multiple Genes Contributing to Vi Capsular Expression in Salmonella enterica Serovar Typhi.Pickard D, Kingsley RA, Hale C, Turner K, Sivaraman K, Wetter M, Langridge G, Dougan G. J Bacteriol. 2013 Mar;195(6):1320-6.

Composition, acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7. Pickard D, Wain J, Baker S, Line A, Chohan S, Fookes M, Barron A, Gaora PO, Chabalgoity JA, Thanky N, Scholes C, Thomson N, Quail M, Parkhill J, Dougan G.J Bacteriol. 2003 Sep;185(17):5055-65.

Characterisation and distribution of a cryptic Salmonella typhi plasmid pHCM2.

Kidgell C, Pickard D, Wain J, James K, Diem Nga LT, Diep TS, Levine MM, O'Gaora P, Prentice MB, Parkhill J, Day N, Farrar J, Dougan G. Plasmid. 2002 May;47(3):159-71. doi: 10.1016/s0147-619x(02)00013-6. PMID: 12151231

Characterization of defined ompR mutants of Salmonella typhi: ompR is involved in the regulation of Vi polysaccharide expression.

Pickard D, Li J, Roberts M, Maskell D, Hone D, Levine M, Dougan G, Chatfield S. Infect Immun. 1994 Sep;62(9):3984-93. doi: 10.1128/IAI.62.9.3984-3993.1994. PMID: 8063417

Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis. Charles IG, Dougan G, Pickard D, Chatfield S, Smith M, Novotny P, Morrissey P, Fairweather NF. Proc Natl Acad Sci U S A. 1989 May;86(10):3554-8. doi: 10.1073/pnas.86.10.3554. PMID: 2542937

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