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. There are currently over 100 ongoing projects and Julian's team collaborates widely within the UK and world scientific community. Previously, the group has generated reference genomes of organisms that are of fundamental importance for human health, including the causative agents of tuberculosis, plague, typhoid fever, whooping cough, 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 Gram positive bacteria like Staphylococcus and Streptococcus. 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.

"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 Clostridium difficile). This area is being greatly facilitated by the new ultra-high throughput sequencing technologies, and we are working with colleagues in Addenbrooke's Hospital to learn how to apply these approaches to clinical microbiology.

Laboratory studies - transcriptomics, proteomics, mutagenesis, microbiota

Julian's team also apply multiple lab-based approaches for organisms that they are studying in-depth.

These include transcriptome studies using 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. They also rely heavily on the support of the core sequencing and informatics teams.

Informatics

To support their 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 tools. 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 data 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 run a series of bioinformatics training workshops in developing countries such as Vietnam, Thailand, Malawi, Uraguay, Costa Rica and Kenya.

Selected Recent Publications

Google Scholar

ResearcherID G-4703-2011

ORCID 0000-0002-7069-5958

• Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans.

  Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, Parkhill J, Malla B, Berg S, Thwaites G, Yeboah-Manu D, Bothamley G, Mei J, Wei L, Bentley S, Harris SR, Niemann S, Diel R, Aseffa A, Gao Q, Young D and Gagneux S

  Nature genetics 2013;45;10;1176-82

  PUBMED: 23995134; DOI: 10.1038/ng.2744

• What has high-throughput sequencing ever done for us?

  Parkhill J

  Nature reviews. Microbiology 2013;11;10;664-5

  PUBMED: 23979431; DOI: 10.1038/nrmicro3112

• Distinguishable Epidemics of Multidrug-Resistant Salmonella Typhimurium DT104 in Different Hosts.

  Mather AE, Reid SW, Maskell DJ, Parkhill J, Fookes MC, Harris SR, Brown DJ, Coia JE, Mulvey MR, Gilmour MW, Petrovska L, de Pinna E, Kuroda M, Akiba M, Izumiya H, Connor TR, Suchard MA, Lemey P, Mellor DJ, Haydon DT and Thomson NR

  Science (New York, N.Y.) 2013

  PUBMED: 24030491; DOI: 10.1126/science.1240578

• Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis.

  Köser CU, Bryant JM, Becq J, Török ME, Ellington MJ, Marti-Renom MA, Carmichael AJ, Parkhill J, Smith GP and Peacock SJ

  The New England journal of medicine 2013;369;3;290-2

  PUBMED: 23863072; DOI: 10.1056/NEJMc1215305

• Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter.

  Sheppard SK, Didelot X, Meric G, Torralbo A, Jolley KA, Kelly DJ, Bentley SD, Maiden MC, Parkhill J and Falush D

  Proceedings of the National Academy of Sciences of the United States of America 2013;110;29;11923-7

  PUBMED: 23818615; PMC: 3718156; DOI: 10.1073/pnas.1305559110

• Rapid Bacterial Whole-Genome Sequencing to Enhance Diagnostic and Public Health Microbiology.

  Reuter S, Ellington MJ, Cartwright EJ, Köser CU, Török ME, Gouliouris T, Harris SR, Brown NM, Holden MT, Quail M, Parkhill J, Smith GP, Bentley SD and Peacock SJ

  JAMA internal medicine 2013

  PUBMED: 23857503; DOI: 10.1001/jamainternmed.2013.7734

• Population genomics of post-vaccine changes in pneumococcal epidemiology.

  Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM, Parkhill J, Bentley SD, Hanage WP and Lipsitch M

  Nature genetics 2013;45;6;656-63

  PUBMED: 23644493; PMC: 3725542; DOI: 10.1038/ng.2625

• Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study.

  Bryant JM, Grogono DM, Greaves D, Foweraker J, Roddick I, Inns T, Reacher M, Haworth CS, Curran MD, Harris SR, Peacock SJ, Parkhill J and Floto RA

  Lancet 2013;381;9877;1551-60

  PUBMED: 23541540; PMC: 3664974; DOI: 10.1016/S0140-6736(13)60632-7

• Whole-genome sequences of Chlamydia trachomatis directly from clinical samples without culture.

  Seth-Smith HM, Harris SR, Skilton RJ, Radebe FM, Golparian D, Shipitsyna E, Duy PT, Scott P, Cutcliffe LT, O'Neill C, Parmar S, Pitt R, Baker S, Ison CA, Marsh P, Jalal H, Lewis DA, Unemo M, Clarke IN, Parkhill J and Thomson NR

  Genome research 2013;23;5;855-66

  PUBMED: 23525359; PMC: 3638141; DOI: 10.1101/gr.150037.112

• A comparison of dense transposon insertion libraries in the Salmonella serovars Typhi and Typhimurium.

  Barquist L, Langridge GC, Turner DJ, Phan MD, Turner AK, Bateman A, Parkhill J, Wain J and Gardner PP

  Nucleic acids research 2013;41;8;4549-64

  PUBMED: 23470992; PMC: 3632133; DOI: 10.1093/nar/gkt148

• A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.

  Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, Strommenger B, Layer F, Witte W, de Lencastre H, Skov R, Westh H, Zemlicková H, Coombs G, Kearns AM, Hill RL, Edgeworth J, Gould I, Gant V, Cooke J, Edwards GF, McAdam PR, Templeton KE, McCann A, Zhou Z, Castillo-Ramírez S, Feil EJ, Hudson LO, Enright MC, Balloux F, Aanensen DM, Spratt BG, Fitzgerald JR, Parkhill J, Achtman M, Bentley SD and Nübel U

  Genome research 2013;23;4;653-64

  PUBMED: 23299977; PMC: 3613582; DOI: 10.1101/gr.147710.112

• Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions.

  Adler CJ, Dobney K, Weyrich LS, Kaidonis J, Walker AW, Haak W, Bradshaw CJ, Townsend G, Sołtysiak A, Alt KW, Parkhill J and Cooper A

  Nature genetics 2013;45;4;450-5, 455e1

  PUBMED: 23416520; DOI: 10.1038/ng.2536

• Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data.

  Bryant JM, Schürch AC, van Deutekom H, Harris SR, de Beer JL, de Jager V, Kremer K, van Hijum SA, Siezen RJ, Borgdorff M, Bentley SD, Parkhill J and van Soolingen D

  BMC infectious diseases 2013;13;1;110

  PUBMED: 23446317; PMC: 3599118; DOI: 10.1186/1471-2334-13-110

• Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study.

  Harris SR, Cartwright EJ, Török ME, Holden MT, Brown NM, Ogilvy-Stuart AL, Ellington MJ, Quail MA, Bentley SD, Parkhill J and Peacock SJ

  The Lancet infectious diseases 2013;13;2;130-6

  PUBMED: 23158674; PMC: 3556525; DOI: 10.1016/S1473-3099(12)70268-2

• Emergence and global spread of epidemic healthcare-associated Clostridium difficile.

  He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, D'Arc S, Brazier J, Brown D, Coia JE, Douce G, Gerding D, Kim HJ, Koh TH, Kato H, Senoh M, Louie T, Michell S, Butt E, Peacock SJ, Brown NM, Riley T, Songer G, Wilcox M, Pirmohamed M, Kuijper E, Hawkey P, Wren BW, Dougan G, Parkhill J and Lawley TD

  Nature genetics 2013;45;1;109-13

  PUBMED: 23222960; PMC: 3605770; DOI: 10.1038/ng.2478

• Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa.

  Okoro CK, Kingsley RA, Connor TR, Harris SR, Parry CM, Al-Mashhadani MN, Kariuki S, Msefula CL, Gordon MA, de Pinna E, Wain J, Heyderman RS, Obaro S, Alonso PL, Mandomando I, MacLennan CA, Tapia MD, Levine MM, Tennant SM, Parkhill J and Dougan G

  Nature genetics 2012;44;11;1215-21

  PUBMED: 23023330; PMC: 3491877; DOI: 10.1038/ng.2423

• 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

• Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

  Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, Goulding D, Rad R, Schreiber F, Brandt C, Deakin LJ, Pickard DJ, Duncan SH, Flint HJ, Clark TG, Parkhill J and Dougan G

  PLoS pathogens 2012;8;10;e1002995

  PUBMED: 23133377; PMC: 3486913; DOI: 10.1371/journal.ppat.1002995

• 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; PMC: 3736323; 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; PMC: 3728647; 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; PMC: 3648787; 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

• Helminth genomes
• Global health research