Lawley Lab | Host-microbiota interactions

Lawley Lab | Host-microbiota interactions

Lawley Lab

lawleylab2017.pngSanger Institute, Genome Research Limited

Our Research and Approach

We are covered with a complex microbial community, known as our microbiota, which plays important roles in our physiology, immunity, metabolism and sustenance. Within the human gastrointestinal tract alone there are over 1,000 bacterial species, which amounts to approximately 10 times more cells than we harbor in our entire body and 200 times more genes than are found within our genome. We are really a 'supraorganism' consisting of our 'human' and 'microbial' selves.

Remarkably, the majority of microbes found within our microbiota have not been cultured, nor described. This is a major limitation for phenotypic and mechanistic studies to understand the basic functions of our microbiota in determining the host's health or disease status. We still have a lot to understand about ourselves and the functions of our human genome in controlling our surroundings in terms of our microbiota. Investigating and understanding these situations raise the possibility that targeting the restoration of a dysbiotic microbiota back to a healthy population mix by using defined formulations of health-associated bacteria could protect against, or treat, certain diseases.

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People

Dr Trevor Lawley
Group Leader

Trevor's research investigates the mechanisms that underlie how micro-organisms on mucosal surfaces (gut, nasopharnyx, uro-gential tract) interact with their host during periods of health and disease. In particular he seeks to develop novel ways to treat diseases that are associated with unwanted imbalances in the micro-organism communities.

Zhu, Ana

Zhu, Ana
Ana Zhu
Postdoctoral fellow

Key Projects, Collaborations, Tools & Data

Research Programmes

Partners and Funders

The Group has several productive internal and external collaborations including those with Professor Fiona Powrie's Group at the University of Oxford, Professor Brendan Wren's Group at London School of Hygiene & Tropical Medicine (LSHTM) and Professor Neil Fairweather's Group at Imperial College London, Open Targets, Arthur Kaser and Matt Zilbauer at the University of Cambridge, Life Study, Lindsay Hall at the University of East Anglia, Alan Walker at the University of Aberdeen, Prof. Ed Kuijper at Leiden University Medical Centre, as well as close interactions with several NHS hospitals and the Health Protection Agency reference laboratories within the UK and abroad.
Internal Partners

Publications

  • Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation.

    Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA et al.

    Nature 2016;533;7604;543-546

  • HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes.

    Forster SC, Browne HP, Kumar N, Hunt M, Denise H et al.

    Nucleic acids research 2016;44;D1;D604-9

  • Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence.

    Kumar N, Miyajima F, He M, Roberts P, Swale A et al.

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016;62;6;746-752

  • Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al.

    Cell host & microbe 2014;16;4;504-16

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

    Lawley TD, Clare S, Walker, Stares MD, Connor TR et al.

    PLoS pathogens 2012;8;10;e1002995

  • Commensal Koch's postulates: establishing causation in human microbiota research.

    Neville BA, Forster SC and Lawley TD

    Current opinion in microbiology 2017;42;47-52

  • DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome.

    Howell KJ, Kraiczy J, Nayak KM, Gasparetto M, Ross A et al.

    Gastroenterology 2017

  • Illuminating microbial diversity.

    Forster SC

    Nature reviews. Microbiology 2017;15;10;578

  • Transmission of the gut microbiota: spreading of health.

    Browne HP, Neville BA, Forster SC and Lawley TD

    Nature reviews. Microbiology 2017;15;9;531-543

  • The essential genomic landscape of the commensal Bifidobacterium breve UCC2003.

    Ruiz L, Bottacini F, Boinett CJ, Cain AK, O'Connell-Motherway M et al.

    Scientific reports 2017;7;1;5648

  • Prevalence of M75 Streptococcus pyogenes Strains Harboring slaA Gene in Patients Affected by Pediatric Obstructive Sleep Apnea Syndrome in Central Italy.

    Viciani E, Montagnani F, Tordini G, Romano A, Salerni L et al.

    Frontiers in microbiology 2017;8;294

  • Comparative genome analysis and global phylogeny of the toxin variant Clostridium difficile PCR Ribotype 017 reveals the evolution of two independent sub-lineages.

    Cairns MD, Preston MD, Hall CL, Gerding DN, Hawkey PM et al.

    Journal of clinical microbiology 2016

  • Evaluation of PacBio sequencing for full-length bacterial 16S rRNA gene classification.

    Wagner J, Coupland P, Browne HP, Lawley TD, Francis SC and Parkhill J

    BMC microbiology 2016;16;1;274

  • Whole genome sequencing of emerging multidrug resistant Candida auris isolates in India demonstrates low genetic variation.

    Sharma C, Kumar N, Pandey R, Meis JF and Chowdhary A

    New microbes and new infections 2016;13;77-82

  • Antibiotics, gut bugs and the young.

    Browne H

    Nature reviews. Microbiology 2016;14;6;336

  • Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation.

    Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA et al.

    Nature 2016;533;7604;543-546

  • Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence.

    Kumar N, Miyajima F, He M, Roberts P, Swale A et al.

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016;62;6;746-752

  • Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism.

    Fung TC, Bessman NJ, Hepworth MR, Kumar N, Shibata N et al.

    Immunity 2016;44;3;634-46

  • Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes.

    O Sheridan P, Martin JC, Lawley TD, Browne HP, Harris HM et al.

    Microbial genomics 2016;2;2;e000043

  • HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes.

    Forster SC, Browne HP, Kumar N, Hunt M, Denise H et al.

    Nucleic acids research 2016;44;D1;D604-9

  • The pig X and Y Chromosomes: structure, sequence, and evolution.

    Skinner BM, Sargent CA, Churcher C, Hunt T, Herrero J et al.

    Genome research 2016;26;1;130-9

  • Analysis of TcdB Proteins within the Hypervirulent Clade 2 Reveals an Impact of RhoA Glucosylation on Clostridium difficile Proinflammatory Activities.

    Quesada-Gómez C, López-Ureña D, Chumbler N, Kroh HK, Castro-Peña C et al.

    Infection and immunity 2016;84;3;856-65

  • Pathogen Resistance Mediated by IL-22 Signaling at the Epithelial-Microbiota Interface.

    Schreiber F, Arasteh JM and Lawley TD

    Journal of molecular biology 2015;427;23;3676-82

  • Genomic Epidemiology of a Protracted Hospital Outbreak Caused by a Toxin A-Negative Clostridium difficile Sublineage PCR Ribotype 017 Strain in London, England.

    Cairns MD, Preston MD, Lawley TD, Clark TG, Stabler RA and Wren BW

    Journal of clinical microbiology 2015;53;10;3141-7

  • Candida albicans commensalism in the gastrointestinal tract.

    Neville BA, d'Enfert C and Bougnoux ME

    FEMS yeast research 2015

  • Defining the Roles of TcdA and TcdB in Localized Gastrointestinal Disease, Systemic Organ Damage, and the Host Response during Clostridium difficile Infections.

    Carter GP, Chakravorty A, Pham Nguyen TA, Mileto S, Schreiber F et al.

    mBio 2015;6;3;e00551

  • As Clear as Mud? Determining the Diversity and Prevalence of Prophages in the Draft Genomes of Estuarine Isolates of Clostridium difficile.

    Hargreaves KR, Otieno JR, Thanki A, Blades MJ, Millard AD et al.

    Genome biology and evolution 2015;7;7;1842-55

  • Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci.

    Couchman EC, Browne HP, Dunn M, Lawley TD, Songer JG et al.

    BMC genomics 2015;16;392

  • Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury.

    Seo SU, Kamada N, Muñoz-Planillo R, Kim YG, Kim D et al.

    Immunity 2015;42;4;744-55

  • Emergence of an outbreak-associated Clostridium difficile variant with increased virulence.

    Quesada-Gómez C, López-Ureña D, Acuña-Amador L, Villalobos-ZĂșñiga M, Du T et al.

    Journal of clinical microbiology 2015;53;4;1216-26

  • High-throughput analysis of gene essentiality and sporulation in Clostridium difficile.

    Dembek M, Barquist L, Boinett CJ, Cain AK, Mayho M et al.

    mBio 2015;6;2;e02383

  • Detection and genomic characterization of motility in Lactobacillus curvatus: confirmation of motility in a species outside the Lactobacillus salivarius clade.

    Cousin FJ, Lynch SM, Harris HM, McCann A, Lynch DB et al.

    Applied and environmental microbiology 2015;81;4;1297-1308

  • Complete genome sequence of the Clostridium difficile laboratory strain 630Δerm reveals differences from strain 630, including translocation of the mobile element CTn5.

    van Eijk E, Anvar SY, Browne HP, Leung WY, Frank J et al.

    BMC genomics 2015;16;31

  • A modified R-type bacteriocin specifically targeting Clostridium difficile prevents colonization of mice without affecting gut microbiota diversity.

    Gebhart D, Lok S, Clare S, Tomas M, Stares M et al.

    mBio 2015;6;2

  • Bacterial genospecies that are not ecologically coherent: population genomics of Rhizobium leguminosarum.

    Kumar N, Lad G, Giuntini E, Kaye ME, Udomwong P et al.

    Open biology 2015;5;1;140133

  • Complete genome sequence of BS49 and draft genome sequence of BS34A, Bacillus subtilis strains carrying Tn916.

    Browne HP, Anvar SY, Frank J, Lawley TD, Roberts AP and Smits WK

    FEMS microbiology letters 2015;362;3;1-4

  • MicroRNA as Type I Interferon-Regulated Transcripts and Modulators of the Innate Immune Response.

    Forster SC, Tate MD and Hertzog PJ

    Frontiers in immunology 2015;6;334

  • Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors.

    Sarvestani ST, Stunden HJ, Behlke MA, Forster SC, McCoy CE et al.

    Nucleic acids research 2015;43;2;1177-88

  • Systematic discovery of probiotics.

    Forster SC and Lawley TD

    Nature biotechnology 2015;33;1;47-9

  • Third Report on Chicken Genes and Chromosomes 2015.

    Schmid M, Smith J, Burt DW, Aken BL, Antin PB et al.

    Cytogenetic and genome research 2015;145;2;78-179

  • Pathogens' exploitation of the intestinal food web.

    Pham N TA and Lawley TD

    Cell host & microbe 2014;16;6;703-5

  • Whole genome sequencing reveals potential spread of Clostridium difficile between humans and farm animals in the Netherlands, 2002 to 2011.

    Knetsch CW, Connor TR, Mutreja A, van Dorp SM, Sanders IM et al.

    Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2014;19;45;20954

  • Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al.

    Cell host & microbe 2014;16;4;504-16

  • Genomic analysis of the causative agents of coccidiosis in domestic chickens.

    Reid AJ, Blake DP, Ansari HR, Billington K, Browne HP et al.

    Genome research 2014;24;10;1676-85

  • Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV.

    Stacey MA, Marsden M, Pham N TA, Clare S, Dolton G et al.

    Cell host & microbe 2014;15;4;471-83

  • Vying over spilt oil.

    Pham N TA and Anonye BO

    Nature reviews. Microbiology 2014;12;3;156

  • Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism.

    Pettit LJ, Browne HP, Yu L, Smits WK, Fagan RP et al.

    BMC genomics 2014;15;160

  • Emerging insights on intestinal dysbiosis during bacterial infections.

    Pham TA and Lawley TD

    Current opinion in microbiology 2014;17;67-74

  • Abundant and diverse clustered regularly interspaced short palindromic repeat spacers in Clostridium difficile strains and prophages target multiple phage types within this pathogen.

    Hargreaves KR, Flores CO, Lawley TD and Clokie MR

    mBio 2014;5;5;e01045-13

  • IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage.

    Cheon H, Holvey-Bates EG, Schoggins JW, Forster S, Hertzog P et al.

    The EMBO journal 2013;32;20;2751-63

  • Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium difficile infection.

    Adamu BO and Lawley TD

    Current opinion in microbiology 2013;16;5;596-601

  • Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1.

    de Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA et al.

    Nature immunology 2013;14;9;901-7

  • Eph receptor signaling and ephrins.

    Lisabeth EM, Falivelli G and Pasquale EB

    Cold Spring Harbor perspectives in biology 2013;5;9

  • The agr locus regulates virulence and colonization genes in Clostridium difficile 027.

    Martin MJ, Clare S, Goulding D, Faulds-Pain A, Barquist L et al.

    Journal of bacteriology 2013;195;16;3672-81

  • Helicobacter pylori VacA suppresses Lactobacillus acidophilus-induced interferon beta signaling in macrophages via alterations in the endocytic pathway.

    Weiss G, Forster S, Irving A, Tate M, Ferrero RL et al.

    mBio 2013;4;3;e00609-12

  • The zebrafish reference genome sequence and its relationship to the human genome.

    Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C et al.

    Nature 2013;496;7446;498-503

  • RNA-eXpress annotates novel transcript features in RNA-seq data.

    Forster SC, Finkel AM, Gould JA and Hertzog PJ

    Bioinformatics (Oxford, England) 2013;29;6;810-2

  • Proteomic comparison of historic and recently emerged hypervirulent Clostridium difficile strains.

    Chen JW, Scaria J, Mao C, Sobral B, Zhang S et al.

    Journal of proteome research 2013;12;3;1151-61

  • SpoIVA and SipL are Clostridium difficile spore morphogenetic proteins.

    Putnam EE, Nock AM, Lawley TD and Shen A

    Journal of bacteriology 2013;195;6;1214-25

  • Therapeutic modulation of intestinal dysbiosis.

    Walker AW and Lawley TD

    Pharmacological research 2013;69;1;75-86

  • Current application and future perspectives of molecular typing methods to study Clostridium difficile infections.

    Knetsch CW, Lawley TD, Hensgens MP, Corver J, Wilcox MW and Kuijper EJ

    Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2013;18;4;20381

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

    He M, Miyajima F, Roberts P, Ellison L, Pickard DJ et al.

    Nature genetics 2013;45;1;109-13

  • Global analysis of the sporulation pathway of Clostridium difficile.

    Fimlaid KA, Bond JP, Schutz KC, Putnam EE, Leung JM et al.

    PLoS genetics 2013;9;8;e1003660

  • Interferome v2.0: an updated database of annotated interferon-regulated genes.

    Rusinova I, Forster S, Yu S, Kannan A, Masse M et al.

    Nucleic acids research 2013;41;Database issue;D1040-6

  • Intestinal colonization resistance.

    Lawley TD and Walker AW

    Immunology 2013;138;1;1-11

  • Protective activity of the CnaBE3 domain conserved among Staphylococcus aureus Sdr proteins.

    Becherelli M, Prachi P, Viciani E, Biagini M, Fiaschi L et al.

    PloS one 2013;8;9;e74718

  • Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking and ATF6 activation.

    Falivelli G, De Jaco A, Favaloro FL, Kim H, Wilson J et al.

    Human molecular genetics 2012;21;21;4761-73

  • The Clostridium difficile spo0A gene is a persistence and transmission factor.

    Deakin LJ, Clare S, Fagan RP, Dawson LF, Pickard DJ et al.

    Infection and immunity 2012;80;8;2704-11

  • Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.

    Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y et al.

    Nature medicine 2012;18;8;1224-31

  • Interferon signatures in immune disorders and disease.

    Forster S

    Immunology and cell biology 2012;90;5;520-7

  • The ancillary protein 1 of Streptococcus pyogenes FCT-1 pili mediates cell adhesion and biofilm formation through heterophilic as well as homophilic interactions.

    Becherelli M, Manetti AG, Buccato S, Viciani E, Ciucchi L et al.

    Molecular microbiology 2012;83;5;1035-47

  • Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species.

    Jackson AP, Berry A, Aslett M, Allison HC, Burton P et al.

    Proceedings of the National Academy of Sciences of the United States of America 2012;109;9;3416-21

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

    Lawley TD, Clare S, Walker, Stares MD, Connor TR et al.

    PLoS pathogens 2012;8;10;e1002995

  • Population genomics of Sinorhizobium medicae based on low-coverage sequencing of sympatric isolates.

    Bailly X, Giuntini E, Sexton MC, Lower RP, Harrison PW et al.

    The ISME journal 2011;5;11;1722-34

  • Carbohydrate catabolic flexibility in the mammalian intestinal commensal Lactobacillus ruminis revealed by fermentation studies aligned to genome annotations.

    O'Donnell MM, Forde BM, Neville B, Ross PR and O'Toole PW

    Microbial cell factories 2011;10 Suppl 1;S12

  • Genome sequences and comparative genomics of two Lactobacillus ruminis strains from the bovine and human intestinal tracts.

    Forde BM, Neville BA, O'Donnell MM, Riboulet-Bisson E, Claesson MJ et al.

    Microbial cell factories 2011;10 Suppl 1;S13

  • Modernizing reference genome assemblies.

    Church DM, Schneider VA, Graves T, Auger K, Cunningham F et al.

    PLoS biology 2011;9;7;e1001091

  • Systems biology of interferon responses.

    Hertzog P, Forster S and Samarajiwa S

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2011;31;1;5-11

  • Toll-like receptors as interferon-regulated genes and their role in disease.

    Khoo JJ, Forster S and Mansell A

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2011;31;1;13-25

  • Use of purified Clostridium difficile spores to facilitate evaluation of health care disinfection regimens.

    Lawley TD, Clare S, Deakin LJ, Goulding D, Yen JL et al.

    Applied and environmental microbiology 2010;76;20;6895-900

  • Probiotic properties of Lactobacillus salivarius and closely related Lactobacillus species.

    Neville BA and O'Toole PW

    Future microbiology 2010;5;5;759-74

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

    He M, Sebaihia M, Lawley TD, Stabler RA, Dawson LF et al.

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

  • Fas gene polymorphisms in systemic lupus erythematosus and serum levels of some apoptosis-related molecules.

    Arasteh JM, Araste JM, Sarvestani EK, Aflaki E and Amirghofran Z

    Immunological investigations 2010;39;1;27-38

  • Antibiotic treatment of clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts.

    Lawley TD, Clare S, Walker AW, Goulding D, Stabler RA et al.

    Infection and immunity 2009;77;9;3661-9

  • Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores.

    Lawley TD, Croucher NJ, Yu L, Clare S, Sebaihia M et al.

    Journal of bacteriology 2009;191;17;5377-86

  • TBrowse: an integrative genomics map of Mycobacterium tuberculosis.

    Bhardwaj A, Bhartiya D, Kumar N, Open Source Drug Discovery Consortium and Scaria V

    Tuberculosis (Edinburgh, Scotland) 2009;89;5;386-7

  • Regulation of tomato Prf by Pto-like protein kinases.

    Mucyn TS, Wu AJ, Balmuth AL, Arasteh JM and Rathjen JP

    Molecular plant-microbe interactions : MPMI 2009;22;4;391-401

  • Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium.

    Stabler RA, He M, Dawson L, Martin M, Valiente E et al.

    Genome biology 2009;10;9;R102

  • INTERFEROME: the database of interferon regulated genes.

    Samarajiwa SA, Forster S, Auchettl K and Hertzog PJ

    Nucleic acids research 2009;37;Database issue;D852-7

  • The DNA sequence and biological annotation of human chromosome 1.

    Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D et al.

    Nature 2006;441;7091;315-21

  • Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse.

    Lawley TD, Chan K, Thompson LJ, Kim CC, Govoni GR and Monack DM

    PLoS pathogens 2006;2;2;e11

  • The DNA sequence of the human X chromosome.

    Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K et al.

    Nature 2005;434;7031;325-37

  • The DNA sequence and comparative analysis of human chromosome 10.

    Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L et al.

    Nature 2004;429;6990;375-81

  • DNA sequence and analysis of human chromosome 9.

    Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE et al.

    Nature 2004;429;6990;369-74

  • The DNA sequence and analysis of human chromosome 13.

    Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL et al.

    Nature 2004;428;6982;522-8

  • The DNA sequence and analysis of human chromosome 6.

    Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL et al.

    Nature 2003;425;6960;805-11

  • The DNA sequence and comparative analysis of human chromosome 20.

    Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG et al.

    Nature 2001;414;6866;865-71

  • Initial sequencing and analysis of the human genome.

    Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al.

    Nature 2001;409;6822;860-921