Dr Julian Parkhill

Julian uses high throughput sequencing and phenotyping to study pathogen diversity and variation, how they affect virulence and transmission, and what they tell us about the evolution of pathogenicity and host interactions.

Julian's role as Director of Sequencing is primarily strategic: providing a link between the Wellcome Trust Sanger Institute faculty and the sequencing division as well as giving a strategic direction to the sequencing groups.

His primary scientific interest is in Pathogen Genomics, in which we use genome sequencing and analysis to investigate a wide range of human and animal pathogens, ranging from human and bacterial viruses, through to bacteria and protist parasites to multicellular worms. There are currently over 100 ongoing projects and Julian's team collaborates widely within the UK and world scientific community to generate the best possible biological interpretation of the data. The Institute has sequenced the genomes of organisms that are of fundamental importance for human health, including the causative agents of tuberculosis, malaria, plague, typhoid fever, sleeping sickness, whooping cough, dengue fever, leprosy, diphtheria and meningitis.

Genome sequencing and analysis

The team's approach to pathogen genome analysis is "broad and deep". "Broad" means that they are interested in a wide variety of human and animal pathogens, in order to study the wide diversity of mechanisms that are used to infect a host and cause disease. These broad analyses include, for example, related members of a group of organisms that can cause disease in humans, animals and even plants as well as those that can live in a host without causing disease. Comparisons such as these allow us to identify genes that are core to the organism, in terms of specifying common functions, and those that are accessory - responsible for interaction with specific hosts or for causing specific pathologies. Examples of such analysis include the enteric bacteria such as Salmonella, Escherichia, Yersinia and Erwinia, and the parasites Trypanosoma and Leishmania. Broad investigations also allow the team to find the novel and unexpected in less well-studied pathogens and to lay the foundations for genome-enabled science in neglected diseases such as those caused by helminths.

"Deep" refers to multiple comparisons between very closely related strains within a species, or group of species. Such comparisons allow the team to look at the fine detail; how or why do organisms specialise on particular hosts (for example the host-restricted pathogen Salmonella Typhi); how have they evolved (e.g. Bordetella pertussis or Yersinia pestis); how does variation correspond to virulence (e.g. Streptococcus pneumoniae or Neisseria meningitidis). Fine detail comparisons also give the team the markers that allow epidemiological studies of transmission, virulence or drug resistance (for example in, Mycobacterium tuberculosis or Plasmodium falciparum). This area is being greatly facilitated by the new ultra-high throughput sequencing technologies.

Laboratory studies - transcriptomics, proteomics, comparative genomics and bacterial populations

Julian's team often move beyond sequencing and in to lab-based studies for organisms that they are studying in-depth.

These include hybridization-based mechanisms to identify and isolate specific areas of interest from related genomes, transcriptome studies using microarrays and ultra-high-throughput sequencing, proteomic analysis and mutagenesis studies.

Host-associated bacterial populations are of growing interest in terms of their contribution to the health and development of the host. The team are studying bacterial populations, primarily in the gut, in both humans and mice. Looking at how these populations vary between individuals, and between diseased and healthy organs should shed light on the role of microorganisms in these processes.

To pursue these studies effectively, Julian's team have built up strong collaborations with other groups within the Institute, particularly those of Gordon Dougan, John Wain and Dominic Kwiatkowski. The team intends to expand these collaborations to include any new pathogen faculty. They also rely heavily on the support of the core sequencing and informatics teams.

Informatics

To support their pathogen annotation and analysis as well as to present the team's data to the scientific community, they have a small group of programmers working on PSU-specific areas. These include the analysis tool Artemis, which is designed to be an intuitive and portable sequence viewer, as well as a powerful analysis tool and an extension of Artemis, ACT, which allows an interactive view of full genome comparisons. They also have a set of web pages, GeneDB, which serves as a repository and source for our annotation and analysis.

Along with providing it to the scientific community the team believes it is important to enable scientists to utilise their data to its fullest extent in the developing world, where these diseases are most prevalent. In collaboration with the Wellcome Trust Advanced Courses group, Julian's team have begun a series of bioinformatics training workshops in developing countries such as Vietnam, Malawi, Uraguay and Kenya.

Selected Publications

• Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways.

  Thomson NR, Clayton DJ, Windhorst D, Vernikos G, Davidson S, Churcher C, Quail MA, Stevens M, Jones MA, Watson M, Barron A, Layton A, Pickard D, Kingsley RA, Bignell A, Clark L, Harris B, Ormond D, Abdellah Z, Brooks K, Cherevach I, Chillingworth T, Woodward J, Norberczak H, Lord A, Arrowsmith C, Jagels K, Moule S, Mungall K, Sanders M, Whitehead S, Chabalgoity JA, Maskell D, Humphrey T, Roberts M, Barrow PA, Dougan G and Parkhill J

  Genome research 2008;18;10;1624-37

  PUBMED: 18583645; DOI: 10.1101/gr.077404.108; PMC: 2556274

• Replacement of adenylate cyclase toxin in a lineage of Bordetella bronchiseptica.

  Buboltz AM, Nicholson TL, Parette MR, Hester SE, Parkhill J and Harvill ET

  Journal of bacteriology 2008;190;15;5502-11

  PUBMED: 18556799; DOI: 10.1128/JB.00226-08; PMC: 2493278

• Genome evolution of Wolbachia strain wPip from the Culex pipiens group.

  Klasson L, Walker T, Sebaihia M, Sanders MJ, Quail MA, Lord A, Sanders S, Earl J, O'Neill SL, Thomson N, Sinkins SP and Parkhill J

  Molecular biology and evolution 2008;25;9;1877-87

  PUBMED: 18550617; DOI: 10.1093/molbev/msn133; PMC: 2515876

• The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants.

  Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A, Sebaihia M, Saunders D, Arrowsmith C, Carver T, Peters N, Adlem E, Kerhornou A, Lord A, Murphy L, Seeger K, Squares R, Rutter S, Quail MA, Rajandream MA, Harris D, Churcher C, Bentley SD, Parkhill J, Thomson NR and Avison MB

  Genome biology 2008;9;4;R74

  PUBMED: 18419807; DOI: 10.1186/gb-2008-9-4-r74; PMC: 2643945

• Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis.

  Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C, Clarke K, Cronin A, Davis P, Goodhead I, Holroyd N, Jagels K, Lord A, Moule S, Mungall K, Norbertczak H, Quail MA, Rabbinowitsch E, Walker D, White B, Whitehead S, Small PL, Brosch R, Ramakrishnan L, Fischbach MA, Parkhill J and Cole ST

  Genome research 2008;18;5;729-41

  PUBMED: 18403782; DOI: 10.1101/gr.075069.107; PMC: 2336800

• Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility.

  Pearson MM, Sebaihia M, Churcher C, Quail MA, Seshasayee AS, Luscombe NM, Abdellah Z, Arrosmith C, Atkin B, Chillingworth T, Hauser H, Jagels K, Moule S, Mungall K, Norbertczak H, Rabbinowitsch E, Walker D, Whithead S, Thomson NR, Rather PN, Parkhill J and Mobley HL

  Journal of bacteriology 2008;190;11;4027-37

  PUBMED: 18375554; DOI: 10.1128/JB.01981-07; PMC: 2395036

• Genome of the actinomycete plant pathogen Clavibacter michiganensis subsp. sepedonicus suggests recent niche adaptation.

  Bentley SD, Corton C, Brown SE, Barron A, Clark L, Doggett J, Harris B, Ormond D, Quail MA, May G, Francis D, Knudson D, Parkhill J and Ishimaru CA

  Journal of bacteriology 2008;190;6;2150-60

  PUBMED: 18192393; DOI: 10.1128/JB.01598-07; PMC: 2258862

• Resolving the structural features of genomic islands: a machine learning approach.

  Vernikos GS and Parkhill J

  Genome research 2008;18;2;331-42

  PUBMED: 18071028; DOI: 10.1101/gr.7004508; PMC: 2203631

• Sequence-based analysis of pQBR103; a representative of a unique, transfer-proficient mega plasmid resident in the microbial community of sugar beet.

  Tett A, Spiers AJ, Crossman LC, Ager D, Ciric L, Dow JM, Fry JC, Harris D, Lilley A, Oliver A, Parkhill J, Quail MA, Rainey PB, Saunders NJ, Seeger K, Snyder LA, Squares R, Thomas CM, Turner SL, Zhang XX, Field D and Bailey MJ

  The ISME journal 2007;1;4;331-40

  PUBMED: 18043644; DOI: 10.1038/ismej.2007.47; PMC: 2656933

• Chlamydia trachomatis: genome sequence analysis of lymphogranuloma venereum isolates.

  Thomson NR, Holden MT, Carder C, Lennard N, Lockey SJ, Marsh P, Skipp P, O'Connor CD, Goodhead I, Norbertzcak H, Harris B, Ormond D, Rance R, Quail MA, Parkhill J, Stephens RS and Clarke IN

  Genome research 2008;18;1;161-71

  PUBMED: 18032721; DOI: 10.1101/gr.7020108; PMC: 2134780