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.

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 transcriptome studies using microarrays and high-throughput sequencing, proteomic analysis and saturation 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, Trevor Lawley 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 pathogen-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

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ResearcherID

• Artemis: an integrated platform for visualization and analysis of high-throughput sequence-based experimental data.

  Carver T, Harris SR, Berriman M, Parkhill J and McQuillan JA

  Bioinformatics (Oxford, England) 2012;28;4;464-9

  PUBMED: 22199388; PMC: 3278759; DOI: 10.1093/bioinformatics/btr703

• Evidence for several waves of global transmission in the seventh cholera pandemic.

  Mutreja A, Kim DW, Thomson NR, Connor TR, Lee JH, Kariuki S, Croucher NJ, Choi SY, Harris SR, Lebens M, Niyogi SK, Kim EJ, Ramamurthy T, Chun J, Wood JL, Clemens JD, Czerkinsky C, Nair GB, Holmgren J, Parkhill J and Dougan G

  Nature 2011;477;7365;462-5

  PUBMED: 21866102; DOI: 10.1038/nature10392

• Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study.

  García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD, Walpole E, Brooks K, Pickard DJ, Teale C, Parkhill J, Bentley SD, Edwards GF, Girvan EK, Kearns AM, Pichon B, Hill RL, Larsen AR, Skov RL, Peacock SJ, Maskell DJ and Holmes MA

  The Lancet infectious diseases 2011;11;8;595-603

  PUBMED: 21641281; DOI: 10.1016/S1473-3099(11)70126-8

• Salmonella bongori provides insights into the evolution of the Salmonellae.

  Fookes M, Schroeder GN, Langridge GC, Blondel CJ, Mammina C, Connor TR, Seth-Smith H, Vernikos GS, Robinson KS, Sanders M, Petty NK, Kingsley RA, Bäumler AJ, Nuccio SP, Contreras I, Santiviago CA, Maskell D, Barrow P, Humphrey T, Nastasi A, Roberts M, Frankel G, Parkhill J, Dougan G and Thomson NR

  PLoS pathogens 2011;7;8;e1002191

  PUBMED: 21876672; PMC: 3158058; DOI: 10.1371/journal.ppat.1002191

• The impact of recombination on dN/dS within recently emerged bacterial clones.

  Castillo-Ramírez S, Harris SR, Holden MT, He M, Parkhill J, Bentley SD and Feil EJ

  PLoS pathogens 2011;7;7;e1002129

  PUBMED: 21779170; PMC: 3136474; DOI: 10.1371/journal.ppat.1002129

• Enterotypes of the human gut microbiome.

  Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J, MetaHIT Consortium, Antolín M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Mérieux A, Melo Minardi R, M'rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD and Bork P

  Nature 2011;473;7346;174-80

  PUBMED: 21508958; DOI: 10.1038/nature09944

• Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities.

  van der Gast CJ, Walker AW, Stressmann FA, Rogers GB, Scott P, Daniels TW, Carroll MP, Parkhill J and Bruce KD

  The ISME journal 2011;5;5;780-91

  PUBMED: 21151003; PMC: 3105771; DOI: 10.1038/ismej.2010.175

• Rapid pneumococcal evolution in response to clinical interventions.

  Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J, van der Linden M, McGee L, von Gottberg A, Song JH, Ko KS, Pichon B, Baker S, Parry CM, Lambertsen LM, Shahinas D, Pillai DR, Mitchell TJ, Dougan G, Tomasz A, Klugman KP, Parkhill J, Hanage WP and Bentley SD

  Science (New York, N.Y.) 2011;331;6016;430-4

  PUBMED: 21273480; DOI: 10.1126/science.1198545

• Bacterial epidemiology and biology--lessons from genome sequencing.

  Parkhill J and Wren BW

  Genome biology 2011;12;10;230

  PUBMED: 22027015; PMC: 3333767; DOI: 10.1186/gb-2011-12-10-230

• Evolutionary dynamics of Clostridium difficile over short and long time scales.

  He M, Sebaihia M, Lawley TD, Stabler RA, Dawson LF, Martin MJ, Holt KE, Seth-Smith HM, Quail MA, Rance R, Brooks K, Churcher C, Harris D, Bentley SD, Burrows C, Clark L, Corton C, Murray V, Rose G, Thurston S, van Tonder A, Walker D, Wren BW, Dougan G and Parkhill J

  Proceedings of the National Academy of Sciences of the United States of America 2010;107;16;7527-32

  PUBMED: 20368420; PMC: 2867753; DOI: 10.1073/pnas.0914322107

• Evolution of MRSA during hospital transmission and intercontinental spread.

  Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA, Edgeworth JD, de Lencastre H, Parkhill J, Peacock SJ and Bentley SD

  Science (New York, N.Y.) 2010;327;5964;469-74

  PUBMED: 20093474; PMC: 2821690; DOI: 10.1126/science.1182395

Related links

• Global health research