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Trevor Lawley

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Trevor Lawley FMedSci is a Faculty member and Group Leader in the Host-Microbiota Interactions Lab at the Wellcome Sanger Institute (WSI). He is also co-founder and Chief Scientific Officer of the biotech company Microbiotica.

During his career, Lawley has pioneered the application of high throughput genomic and culturing approaches to characterise enteric pathogens and investigate the microbiomes contained on and within host organisms, during periods of health and disease.

Education and career

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Lawley received his bachelor's degree in Biology in 1997 from Acadia University. He then studied for a PhD at the University of Alberta, in the laboratories of Diane Taylor and Laura Frost, where he studied the mechanisms that pathogenic bacteria use to disseminate antibiotic resistance genes.[1] After his PhD, Trevor was awarded a Canadian Institutes of Health Research post-doctoral fellowship to work in the Laboratories of Stanley Falkow and Denise Monack at Stanford University, where he studied the impact of antibiotic treatment on Salmonella disease and transmission.[2]

In 2007 Lawley received a Royal Society of London Award to start a research programme on Clostridioides difficile disease and transmission at the Wellcome Sanger Institute. In 2010, he was appointed as a Career Development Fellow in the Sanger Institute Faculty and was promoted to Faculty Group Leader in 2014 and a Senior Group Leader in 2021.

In December 2016, Lawley, together with Gordon Dougan and Mike Romanos, co-founded the biotech company Microbiotica through £12M seed funding from Cambridge Innovation Capital, IP Group and Seventure. In March 2022, Microbiotica secured Series B funding to perform two clinical studies for patients with cancer and ulcerative colitis.[3] Microbiotica develops Live Bacterial Therapeutics, biomarkers and microbiome-based technologies focused on autoimmune diseases and cancers.

Research

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Lawley leads the Host-Microbiota Interactions Lab at the Sanger Institute, which explores the relationship between humans and the bacteria and viruses that collectively form their microbiome.[4]

Lawley and his team use a range of methods and tools, including large scale metagenomic analysis, genetics, mouse and cellular models, state-of-the art microbial culturing, transcriptomics, proteomics and machine learning, to investigate the microbial communities associated with human health and a range of developmental disorders, diseases and poorly understood syndromes. They are particularly interested in how the microbiome influences long-term growth, development and disease resistance of children from Westernized and Low- and Middle-Income countries.

They have worked on concepts, analytical tools, and methodology to enable basic discoveries and translation of medicines and diagnostics from the human microbiome using data-driven and hypothesis-driven approaches.

They focus on several key areas including:

  • Characterising the evolution of taxonomic and functional diversity in the human microbiome;[5][6][7][8][9][10][11]
  • Investigating the early-life microbiome, and how birth-mode and clinical interventions, impact microbiome acquisition and assembly[12][13][14]
  • Understanding host-microbiome interactions and drivers of inflammatory disease and cancer[15][16][17][18]
  • Studying the fundamental biology, transmission and pathogenesis of C. difficile.[19][20][21][22][23][24][25]

Lawley’s group has authored over 100 papers. Their work is regularly covered in the scientific and popular press[26][27]

Awards and honours

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Lawley was elected as a Fellow of the Academy of Medical Sciences in 2023.[28] In 2015 Lawley received the Peggy Lillis Foundation “Innovator Award” for Pioneering Work on Live Biotherapeutics.

References

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  1. ^ Lawley, Trevor (2003). The Life Cycle of the Conjugative Plasmid (PhD thesis) (Thesis). University of Alberta.
  2. ^ https://webapps.cihr-irsc.gc.ca/funding/detail_e?pResearchId=9805600&p_version=CIHR&p_language=E&p_session_id=3266369 [dead link‍]
  3. ^ "Microbiotica ready to cross therapeutic threshold with clinical trials milestone". Cambridge Independent. 2022-07-01. Retrieved 2023-06-22.
  4. ^ "Lawley Lab". www.sanger.ac.uk. Retrieved 2023-10-24.
  5. ^ Camarillo-Guerrero, Luis F.; Almeida, Alexandre; Rangel-Pineros, Guillermo; Finn, Robert D.; Lawley, Trevor D. (February 2021). "Massive expansion of human gut bacteriophage diversity". Cell. 184 (4): 1098–1109.e9. doi:10.1016/j.cell.2021.01.029. PMC 7895897. PMID 33606979.
  6. ^ Beresford-Jones, Benjamin S.; Forster, Samuel C.; Stares, Mark D.; Notley, George; Viciani, Elisa; Browne, Hilary P.; Boehmler, Daniel J.; Soderholm, Amelia T.; Kumar, Nitin; Vervier, Kevin; Cross, Justin R.; Almeida, Alexandre; Lawley, Trevor D.; Pedicord, Virginia A. (January 2022). "The Mouse Gastrointestinal Bacteria Catalogue enables translation between the mouse and human gut microbiotas via functional mapping". Cell Host & Microbe. 30 (1): 124–138.e8. doi:10.1016/j.chom.2021.12.003. PMC 8763404. PMID 34971560.
  7. ^ Browne, Hilary P.; Almeida, Alexandre; Kumar, Nitin; Vervier, Kevin; Adoum, Anne T.; Viciani, Elisa; Dawson, Nicholas J. R.; Forster, Samuel C.; Cormie, Claire; Goulding, David; Lawley, Trevor D. (December 2021). "Host adaptation in gut Firmicutes is associated with sporulation loss and altered transmission cycle". Genome Biology. 22 (1): 204. doi:10.1186/s13059-021-02428-6. ISSN 1474-760X. PMC 8340488. PMID 34348764.
  8. ^ James, Kylie R.; Gomes, Tomas; Elmentaite, Rasa; Kumar, Nitin; Gulliver, Emily L.; King, Hamish W.; Stares, Mark D.; Bareham, Bethany R.; Ferdinand, John R.; Petrova, Velislava N.; Polański, Krzysztof; Forster, Samuel C.; Jarvis, Lorna B.; Suchanek, Ondrej; Howlett, Sarah (2020-03-02). "Distinct microbial and immune niches of the human colon". Nature Immunology. 21 (3): 343–353. doi:10.1038/s41590-020-0602-z. ISSN 1529-2908. PMC 7212050. PMID 32066951.
  9. ^ Almeida, Alexandre; Mitchell, Alex L.; Boland, Miguel; Forster, Samuel C.; Gloor, Gregory B.; Tarkowska, Aleksandra; Lawley, Trevor D.; Finn, Robert D. (2019-04-25). "A new genomic blueprint of the human gut microbiota". Nature. 568 (7753): 499–504. Bibcode:2019Natur.568..499A. doi:10.1038/s41586-019-0965-1. ISSN 0028-0836. PMC 6784870. PMID 30745586.
  10. ^ Forster, Samuel C.; Kumar, Nitin; Anonye, Blessing O.; Almeida, Alexandre; Viciani, Elisa; Stares, Mark D.; Dunn, Matthew; Mkandawire, Tapoka T.; Zhu, Ana; Shao, Yan; Pike, Lindsay J.; Louie, Thomas; Browne, Hilary P.; Mitchell, Alex L.; Neville, B. Anne (February 2019). "A human gut bacterial genome and culture collection for improved metagenomic analyses". Nature Biotechnology. 37 (2): 186–192. doi:10.1038/s41587-018-0009-7. ISSN 1087-0156. PMC 6785715. PMID 30718869.
  11. ^ Browne, Hilary P.; Forster, Samuel C.; Anonye, Blessing O.; Kumar, Nitin; Neville, B. Anne; Stares, Mark D.; Goulding, David; Lawley, Trevor D. (2016-05-26). "Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation". Nature. 533 (7604): 543–546. Bibcode:2016Natur.533..543B. doi:10.1038/nature17645. ISSN 0028-0836. PMC 4890681. PMID 27144353.
  12. ^ Shao, Yan; Forster, Samuel C.; Tsaliki, Evdokia; Vervier, Kevin; Strang, Angela; Simpson, Nandi; Kumar, Nitin; Stares, Mark D.; Rodger, Alison; Brocklehurst, Peter; Field, Nigel; Lawley, Trevor D. (2019-10-03). "Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth". Nature. 574 (7776): 117–121. Bibcode:2019Natur.574..117S. doi:10.1038/s41586-019-1560-1. ISSN 0028-0836. PMC 6894937. PMID 31534227.
  13. ^ Njunge, James M.; Tickell, Kirkby; Diallo, Abdoulaye Hama; Sayeem Bin Shahid, Abu Sadat Mohammad; Gazi, Md. Amran; Saleem, Ali; Kazi, Zaubina; Ali, Syed; Tigoi, Caroline; Mupere, Ezekiel; Lancioni, Christina L.; Yoshioka, Emily; Chisti, Mohammod Jobayer; Mburu, Moses; Ngari, Moses (2022-11-03). "The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia". Gates Open Research. 6: 77. doi:10.12688/gatesopenres.13635.2. ISSN 2572-4754. PMC 9646488. PMID 36415883.
  14. ^ Browne, Hilary P; Shao, Yan; Lawley, Trevor D (October 2022). "Mother–infant transmission of human microbiota". Current Opinion in Microbiology. 69: 102173. doi:10.1016/j.mib.2022.102173. PMID 35785616. S2CID 250239760.
  15. ^ Villemin, Clélia; Six, Anne; Neville, B. Anne; Lawley, Trevor D.; Robinson, Matthew J.; Bakdash, Ghaith (January 2023). "The heightened importance of the microbiome in cancer immunotherapy". Trends in Immunology. 44 (1): 44–59. doi:10.1016/j.it.2022.11.002. PMID 36464584. S2CID 254245428.
  16. ^ Gunjur, Ashray; Manrique-Rincón, Andrea J; Klein, Oliver; Behren, Andreas; Lawley, Trevor D; Welsh, Sarah J; Adams, David J (July 2022). "'Know thyself' – host factors influencing cancer response to immune checkpoint inhibitors". The Journal of Pathology. 257 (4): 513–525. doi:10.1002/path.5907. ISSN 0022-3417. PMC 9320825. PMID 35394069.
  17. ^ Thompson, Nicola A.; Stewart, Grant D.; Welsh, Sarah J.; Doherty, Gary J.; Robinson, Matthew J.; Neville, B. Anne; Vervier, Kevin; Harris, Simon R.; Adams, David J.; Dalchau, Katy; Bruce, David; Demiris, Nikolaos; Lawley, Trevor D.; Corrie, Pippa G. (December 2022). "The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy". BMC Cancer. 22 (1): 99. doi:10.1186/s12885-021-09156-x. ISSN 1471-2407. PMC 8785032. PMID 35073853.
  18. ^ Forster, Samuel C.; Clare, Simon; Beresford-Jones, Benjamin S.; Harcourt, Katherine; Notley, George; Stares, Mark D.; Kumar, Nitin; Soderholm, Amelia T.; Adoum, Anne; Wong, Hannah; Morón, Bélen; Brandt, Cordelia; Dougan, Gordon; Adams, David J.; Maloy, Kevin J. (2022-04-01). "Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis". Nature Microbiology. 7 (4): 590–599. doi:10.1038/s41564-022-01094-z. ISSN 2058-5276. PMC 8975739. PMID 35365791.
  19. ^ Kumar, Nitin; Browne, Hilary P.; Viciani, Elisa; Forster, Samuel C.; Clare, Simon; Harcourt, Katherine; Stares, Mark D.; Dougan, Gordon; Fairley, Derek J.; Roberts, Paul; Pirmohamed, Munir; Clokie, Martha R. J.; Jensen, Mie Birgitte Frid; Hargreaves, Katherine R.; Ip, Margaret (September 2019). "Adaptation of host transmission cycle during Clostridium difficile speciation". Nature Genetics. 51 (9): 1315–1320. doi:10.1038/s41588-019-0478-8. hdl:2436/623457. ISSN 1061-4036. PMID 31406348. S2CID 256819220.
  20. ^ Collins, J.; Robinson, C.; Danhof, H.; Knetsch, C. W.; van Leeuwen, H. C.; Lawley, T. D.; Auchtung, J. M.; Britton, R. A. (January 2018). "Dietary trehalose enhances virulence of epidemic Clostridium difficile". Nature. 553 (7688): 291–294. Bibcode:2018Natur.553..291C. doi:10.1038/nature25178. ISSN 0028-0836. PMC 5984069. PMID 29310122.
  21. ^ Knetsch, C. W.; Kumar, N.; Forster, S. C.; Connor, T. R.; Browne, H. P.; Harmanus, C.; Sanders, I. M.; Harris, S. R.; Turner, L.; Morris, T.; Perry, M.; Miyajima, F.; Roberts, P.; Pirmohamed, M.; Songer, J. G. (March 2018). Fenwick, Brad (ed.). "Zoonotic Transfer of Clostridium difficile Harboring Antimicrobial Resistance between Farm Animals and Humans". Journal of Clinical Microbiology. 56 (3). doi:10.1128/JCM.01384-17. ISSN 0095-1137. PMC 5824051. PMID 29237792.
  22. ^ Kumar, Nitin; Miyajima, Fabio; He, Miao; Roberts, Paul; Swale, Andrew; Ellison, Louise; Pickard, Derek; Smith, Godfrey; Molyneux, Rebecca; Dougan, Gordon; Parkhill, Julian; Wren, Brendan W.; Parry, Christopher M.; Pirmohamed, Munir; Lawley, Trevor D. (2016-03-15). "Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence". Clinical Infectious Diseases. 62 (6): 746–752. doi:10.1093/cid/civ1031. ISSN 1058-4838. PMC 4772841. PMID 26683317.
  23. ^ Fimlaid, Kelly A.; Bond, Jeffrey P.; Schutz, Kristin C.; Putnam, Emily E.; Leung, Jacqueline M.; Lawley, Trevor D.; Shen, Aimee (2013-08-08). Viollier, Patrick H. (ed.). "Global Analysis of the Sporulation Pathway of Clostridium difficile". PLOS Genetics. 9 (8): e1003660. doi:10.1371/journal.pgen.1003660. ISSN 1553-7404. PMC 3738446. PMID 23950727.
  24. ^ He, Miao; Miyajima, Fabio; Roberts, Paul; Ellison, Louise; Pickard, Derek J; Martin, Melissa J; Connor, Thomas R; Harris, Simon R; Fairley, Derek; Bamford, Kathleen B; D'Arc, Stephanie; Brazier, Jon; Brown, Derek; Coia, John E; Douce, Gill (January 2013). "Emergence and global spread of epidemic healthcare-associated Clostridium difficile". Nature Genetics. 45 (1): 109–113. doi:10.1038/ng.2478. ISSN 1061-4036. PMC 3605770. PMID 23222960.
  25. ^ Lawley, Trevor D.; Clare, Simon; Walker, Alan W.; Stares, Mark D.; Connor, Thomas R.; Raisen, Claire; Goulding, David; Rad, Roland; Schreiber, Fernanda; Brandt, Cordelia; Deakin, Laura J.; Pickard, Derek J.; Duncan, Sylvia H.; Flint, Harry J.; Clark, Taane G. (2012-10-25). Gilmore, Michael S. (ed.). "Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice". PLOS Pathogens. 8 (10): e1002995. doi:10.1371/journal.ppat.1002995. ISSN 1553-7374. PMC 3486913. PMID 23133377.
  26. ^ Gallagher, James (25 October 2012). "'Faecal transplant' clue to treating gut bug". BBC. Retrieved 13 June 2023.
  27. ^ Sample, Ian (9 Dec 2012). "Drug-resistant C difficile bug traced to source in US and Canadian hospitals". Retrieved 13 Jun 2023.
  28. ^ "Outstanding biomedical and health researchers elected to Academy of Medical Sciences Fellowship". Academy of Medical Sciences. 18 May 2023. Retrieved 15 November 2023.
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