Professor Philip Butcher is Professor of Molecular Medical Microbiology at St George’s.
He studies bacterial pathogens and their interactions with human and animal hosts by analysing their DNA genome and expression of their genes under different circumstances. In this way, he is improving our knowledge of why bacteria cause disease and helping to develop new diagnostic tests, understanding the development of resistance to antibiotics and identifying new treatments for infection. He has a particular interest in tuberculosis (TB) and gonorrhoea.
His work focuses on the molecular pathogenesis of TB and the use of genomics to facilitate the development of new drugs and diagnostics for it. Since 1999 he has been the Principal Investigator on the BµG@S project, a multi-collaborative microbial pathogen functional genomics resource, originally supported by the Wellcome Trust.
BµG@S developed and provides microarrays for 12 bacterial pathogens, supporting over 100 research groups in the UK and worldwide, resulting in more than 150 publications that address fundamental and applied questions in bacterial pathogenesis. The BµG@S project continues as a self-sustaining research group in translational pathogen genomics, applying whole genome sequencing (WGS) using the IonTorrent Personal Genome Machine next generation DNA sequencer to clinical applications in partnership with the Clinical Microbiology and Infectious Diseases Units at St George’s University Hospitals NHS Foundation Trust.
WGS applications include developing metagenomics for the diagnosis of infectious diseases, informing antibiotic choice in the management of drug resistant tuberculosis (multi drug resistant and extensively drug resistant TB) and investigating genome based molecular epidemiology to inform infection control actions.
His more fundamental research interests include the study of gene expression in Mycobacterium tuberculosis during interaction with host cells such as macrophages and dendritic cellsand directly from human sputum. These studies reveal new insights into the metabolic adaptations of intracellular and in vivo bacteria which may explain the basis of drug tolerance and the need for the prolonged six month treatment regimens for TB. As a partner in the EU FP6 consortium New Medicines for Tuberculosis he provided microarray expertise as enabling technologies in the discovery of a new class of anti-TB drug, the benzothiazinones. He is now a member of the Scientific Advisory Board for the EU FP7 consortium project More Medicines for Tuberculosis. He is also a partner in the TBDUK Tuberculosis Drug Discovery Consortium and the PreDiCT-TB Consortium.
Within a UKCRC Translational Infection Research Initiative consortium - eSTI, Professor Butcher’s other research activities are in the application of species specific microarray-defined DNA probes for the development of point-of-care and self-test devices linked to mobile phones for the diagnosis of sexually transmitted infections. He is also developing tests to discriminate genetic markers for antibiotic resistance in gonorrhoea to aid appropriate antibiotic prescribing and stewardship. The research involves collaborations with multiple Biotech partners and may lead to diagnostic product commercialisation. A new partnership funded by the Technology Strategy Board with the UK based company QuantuMDx is developing a new hand held rapid point of care diagnostic device for tuberculosis and drug resistance testing, which aims to improve access to diagnostics for TB around the world.
Professor Butcher gained his PhD in comparative molecular haematology, studying sickle cell disease, obtained at the Institute of Zoology, London Zoo in 1980. He then continued his career in molecular biology research with postdoctoral positions at King's College London in the Department of Biochemistry studying globin gene expression in bone marrow cells, at St George’s Hospital Medical School in Academic surgery studying the molecular aetiology of human Crohn's disease, and at St Bartholomew's Hospital Medical School working in the Department of Gastroenterology on the parasite Giardia lamblia. He returned to St George's in 1989 as an academic lecturer in medical microbiology and held a number of academic positions leading to appointment of Professor of Molecular Medical Microbiology in 2003
Pond MJ, Nori AV, Witney AA, Lopeman RC, Butcher PD, Sadiq ST. High prevalence of antibiotic resistant Mycoplasma genitalium in non-gonococcal urethritis: the need for routine testing and the inadequacy of current treatment options. Clin Infect Dis. 2014, Jan 2. doi: 10.1093/cid/cit752
Witney A, Gould KA, Pope CF, Bolt F, Stoker NG, Cubbon MD, Bradley CR, Fraise A, Breathnach AS, Butcher PD, Planche TD, Hinds J (2014) Genome sequencing and characterization of an XDR ST111 serotype O12 hospital outbreak strain of Pseudomonas aeruginosa. Clin Microbiol Infect. 2014 Jan 14. doi: 10.1111/1469-0691.12528.
Waddell SJ and Butcher PD. Transcriptomic approaches to mapping responses to drug therapy for tuberculosis. (2013) In: Tuberculosis: Laboratory Diagnosis and Treatment Strategies. Advances in Molecular and Cellular Microbiology Volume 21 (Editor: T. D. McHugh) CABI, 2013. pp.173-183
Witney AA, Waldron DE, Brooks LA, Tyler RH, Withers M, Stoker NG, Wren BW, Butcher PD, Hinds J. BµG@Sbase – a microbial gene expression and comparative genomic database. Nucleic Acids Research. 2012, Jan; 40:D605-609.
Feasey NA, Pond M, Coleman D, Solomon AW, Cosgrove CA, Delgado R, Butcher PD, Mitchison DA, Harrison T. Moxifloxacin and pyrazinamide susceptibility testing in a complex case of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2011, Mar; 15(3): 417-20.
Botella H, Peyron P, Levillain F, Poincloux R, Poquet Y, Brandli I, Wang C, Tailleux L, Tilleul S, Charrière GM, Waddell SJ, Foti M, Lugo-Villarino G, Gao Q, Maridonneau-Parini I, Butcher PD, Castagnoli PR, Gicquel B, de Chastellier C, Neyrolles O. Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe. 2011, 10(3):248-59
Carroll P, Waddell SJ, Butcher PD, Parish T. (2011) Methionine sulfoximine resistance in Mycobacterium tuberculosis is due to a single nucleotide deletion resulting in increased expression of the major glutamine synthetase, GlnA1. Microb Drug Resist. 17(3):351-5.
Makarov V, Manina G, Mikusova K, Möllmann U, Ryabova O, Saint-Joanis B, Dhar N, Pasca MR, Buroni S, Lucarelli AP, Milano A, De Rossi E, Belanova M, Bobovska A, Dianiskova P, Kordulakova J, Sala C, Fullam E, Schneider P, McKinney JD, Brodin P, Christophe T, Waddell S, Butcher P, Albrethsen J, Rosenkrands I, Brosch R, Nandi V, Bharath S, Gaonkar S, Shandil RK, Balasubramanian V, Balganesh T, Tyagi S, Grosset J, Riccardi G and Cole ST. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science. 2009, May 8; 324 (5928): 801-804.
Garton NJ, Waddell SJ, Sherratt AL, Lee S-M, Smith RJ, Senner C, Hinds J, Rajakumar K, Adegbola RA, Besra GS, Butcher PD and Barer MR. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Medicine. 2008, 5(4) 634-645, e75.
Tailleux L, Waddell SJ, Pelizzola M, Mortellaro A, Withers M, Tanne A, Ricciardi-Castagnoli P, Gicquel B, Stoker NG, Butcher PD, Foti M and Neyrolles O. Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages. PLoS ONE. 2008, Jan 2; 3(1): e1403.
Schnappinger D, Ehrt S, Voskuil M, Liu Y, Mangan JA, Monahan IM, Dolganov G, Efron B, Butcher PD, Nathan C and Schoolnik GK. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J.Exp.Med. 2003, 198:693-704.
The BµG@S group comprises:
Dr Jason Hinds (translational applications of pathogen microarrays, genomics and hospital acquired infections, STI diagnostics, enterprise activities);
Dr Adam Witney (bioinformatics, databases and genomics);
Dr Kate Gould (pathogen whole genome sequencing, microarrays, project management);
Dr Denise Waldron (database curating, BµG@Sbase
and Mr Richard Tyler (biocomputing and data analysis tools).
Members of the group working with Professor Butcher on other aspects of his research are:
Dr Jasvir Dhillon (tuberculosis and Mycobacterium ulcerans bacteriology; TSB grant on TB diagnostics with QuantuMDx);
Mr Marcus Pond (eSTI2 consortium with Dr Tariq Sadiq on STI diagnostics and antibiotic resistance; tuberculosis sequencing and diagnostics);
Dr Ken Laing (molecular and genomic technologist).
Professor Butcher is currently co-supervising PhD students both at St George’s and elsewhere:
David Coleman (persistence and antibiotic tolerance in TB - St George's, University of London);
Rebecca Flynn (lysosomal biology in TB with Dr Axel Nohturfft - St George's, University of London);
Dr Clarrisa Oeser (neonatal sepsis genomic aetiology, with Professor Paul Heath, St George's, University of London);
Dr Achyuta Nori (metagenomics of urethritis, with Dr Tariq Sadiq, St George's, University of London);
Sasithon Temisak, (metagenomics, metrology and sepsis, with Dr Foy and Dr Jim Huggett, based at LGC Ltd, Teddington);
Simon Clarke (pathogenesis models of human TB, based at Public Health England, Porton);
Sam Lethbridge (biofilms and antibiotic tolerance in TB, based at Public Health England, Porton).
Beverley Burke (Host gene expression during Chlamydia pneumoniae persistence; St George's, University of London)
Professor Butcher works with colleagues locally and across the UK, in both the public and private sectors. He has been a member of several international consortiums.
At St George's, his collaborators through the BµG@S group include:
Professor Jodi Lindsay, Professor of Microbial Pathogenesis in the Institute of Infection and Immunity (Staphylococcus aureus genome sequencing).
Dr Tim Bull, Institute of Infection and Immunity (Mycobacterium avium subspecies paratuberculosis – comparative genomics);
Professor Tom Harrison, Professor of Infectious Diseases and Medicine (antibiotic resistance in MDR-TB – genome sequencing);
Dr Tim Planche and Dr Matt Lundy, St George’s University Hospitals NHS Foundation Trust Medical Microbiology service (molecular epidemiology of hospital acquired infection outbreak control using clinically timely whole genome sequencing).
Dr Tariq Sadiq and colleagues within the eSTI2 consortium working to develop mobile phone linked PoC diagnostic devices for sexually transmitted infections. This is a multi-intuitional, multi-disciplinary consortium working with multiple commercial companies developing diagnostic platforms.
Elsewhere, his collaborators include:
Dr Joanna Bacon, Public Health England, Porton Down (tuberculosis research);
Professor Timothy McHugh, Professor of Medical Microbiology and Director, Centre for Clinical Biology, University College London;
Professor Michael Barer, Professor of Clinical Microbiology, University of Leicester;
Dr Galina Mukamolova, Lecturer in Microbial Physiology, University of Leicester;
Dr Simon Waddell, Lecturer in Molecular Biochemistry, Brighton and Sussex Medical School;
Professor Butcher also collaborates with colleagues working at QuantuMDx, a company developing hand-held and portable medical devices.
Q-TB: Rapid Point of Care diagnostic and drug susceptibility testing for human tuberculosis. Awarded to P.Butcher, T.Sadiq & S.Krishna. Technology Strategy Board (TSB): Sept 2013 (30 months). (£0.9million)
Exploiting advances in diagnostic and wireless technologies to reduce the burden of sexually transmitted infections in the UK.
Awarded to T Sadiq - principal investigator (PI), P Butcher (co-applicant) et al.
UK Clinical Research Collaboration Translational Infection Research Initiative, Consortium Grant (given via Medical Research Council).
October 2010 to September 2015, £3.9 million
Exploiting advances in diagnostic and wireless technologies to reduce the burden of sexually transmitted infections in the UK.
Awarded to Sadiq, Butcher, Krishna, Griffin (co-PIs).
UK Clinical Research Collaboration Translational Infection Research Initiative, Strategy Development Grant, (given via Medical Research Council).
January 2008 to December 2008, £60,000
New Medicines for tuberculosis (NM4TB).
Awarded to 15 partner organisations, including St George's (P Butcher)
European Commission Integrated Project grant.
January 2006 to January 2011, £450,000
BuG@S-III: translational community support for bacterial microarrays.
Awarded to P Butcher (with J Hinds, NG Stoker and BW Wren).
Wellcome Trust Biomedical resource grant.
May 2009 to June 2011, £398,711
Bacterial transcriptomes and comparative genomics using microarrays – towards a systems biology approach for pathogen biology.
Awarded to P Butcher (with J Hinds, NG Stoker, BW Wren).
November 2006 to April 2009, £585,236
Tuberculosis Drug Discovery-UK (TBD-UK)
Awarded to S Gillespie (principal investigator – UCL), P Butcher (co-applicant) and nine other co-applicants.
Medical Research Council
June 2009 to 2011, £60,000
Development of pan-pathogen microarray detection for sexually transmitted infections and other infections
Awarded to P Butcher, J Hinds and T Sadiq.
Heptagon Fund (London universities enterprise fund); OGT Ltd, Oxford; St George's Path Research Fund and St George's NHS R&D.
October 2007 to 2010, £100,000
Professor Butcher lectures undergraduate students on antibiotics; antibiotic resistance; immune responses to infections; immune evasion strategies; bacterial pathogenesis and toxins; microbiology of the gut and infections of the gut; the scientific basis of vaccines; and practical laboratory based microbiology on investigating infections.
He is a co-organiser for the Life Protection module (infection, immunity, mechanisms of disease) in the Medicine MBBS. Students on the Biomedical Sciences BSc course study this module alongside medical students and Professor Butcher has pioneered joint pathology teaching workshops on the mechanisms of disease.
He supervises third year Biomedical Sciences BSc laboratory research projects on human pathogens, antibiotic resistance and genomics.
He leads the Diagnostic Microbiology module offered to final year students on the Biomedical Sciences BSc course, and to medical students who opt to undertake an intercalated BSc course.
He teaches infection related topics to students on the Physician Assistant Studies Postgraduate Diploma course, and on the Paramedic Science Foundation Degree/BSc Healthcare Practice (Out of Hospital Care Pathway) in the Faculty of Health, Social Care and Education (Kingston University and St George's).
He also teaches St George’s MRes students about tuberculosis.
Professor Butcher is an external examiner for the MSc in Medical Microbiology at the London School of Hygiene and Tropical Medicine.
He has supervised 10 successful PhD projects, one MPhil, one MRes and one MD project in the field of microbiology, infection and tuberculosis.
He currently co-supervises nine PhD projects.
He has examined more than 25 PhD theses for University of London and externally