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Prof Dirk Werling

DrMedVet PhD MRCVS
Professor of Molecular Immunology

Department: Pathobiology and Population Sciences

Campus: Hawkshead

Research Groups: Host-Pathogen Interactions and Vaccinology, IRLFS (Research Programme)

Clinical Groups: Farm Animal Health

Research Centres: RVC Quantitative Biology Resource

My current main research interest is the ontogeny of the innate immune system between species, the importance of SNP in innate immune receptors for ligand binding, and how we can use our knowledge regarding the innate immune system to design new/optimise existing vaccine strategies. Here, we are concentrating more on carbohydrate recogntion and carbohydrate-based vaccines.

After gaining a BSc.VetMed. (Veterinary University Hannover), my Dr.Med.Vet. thesis at the ETH Zuerich examined the impact of Bovine Leukaemia Virus infection on the ability of bovine macrophages to respond to LPS. This work was then followed by a stipend of the Swiss National Science Foundation (SNF) to participate in the PostGraduate course in Experimental Medicine, run by the University Hospital Zuerich. After a year, I returned to ETH Zuerich with a Postdoctoral Research Fellow Stipend of the German Research Foundation (DFG). This was followed by a Marie Curie Research Fellowship of the EU to join the group of Chris Howard at the Institute for Animal Health (Compton Laboratories) to work on the development and characterisation of dendritic cells and their role in respiratory syncytial virus infection. From here, I moved back to the ETH Zuerich as a Senior Scientist (Oberassistent). During this period I expanded the scope of my work to encompass the development of the innate immune system in ruminants, and aspect of pathogen escape mechanisms in innate immune cells. In 2001, I accepted an Assistant Professorship (Tenure Track) at the Institute of Virology (University of Berne), in the group of Thomas Jungi. In 2003, I accepted a Senior Lectureship at the ÐÂÔÂÖ±²¥, and was promoted to a personal tenured Chair and Professor in Molecular Immunology in 2007. The key motivation for this move was the unique opportunity to develop dendritic cell based vaccines for farm animals by targeting the then newly discovered class of innate immune receptors, such as the Toll-like receptors. In this role I have been responsible from the outset for the design, implementation and evaluation of new vaccine delivery platforms. These activities have attracted substantial funding and resulted of the submission of 3 different patent-applications. My research during this period has naturally been biased towards research administration, where close working relationships with industrial partners has been essential. Throughout, however, I have continued to make significant contributions to answering the function of the innate immune response in farm animals and evolutionary questions associated with identified differences between farm animals, human and mice. I have produced so far over 100 Peer Reviewed Publications in international journals across a broad range of empirical research topics such as that of the coevolution between host and pathogens, and the species-specific recognition of pathogens (Trends in Immunology). My current research is funded through BBSRC, EU (FP7 and EMIDA) as well as the Bill and Melinda Gates Foundation.

 

For more information, see:

 

 

Published since January 2018

  1. Holzapfel M, Bonhomme D, Cagliero J, Vernel-Pauillac F, Fanton d'Andon M, Bortolussi S, Fiette L, Goarant C, Wunder EA Jr, Picardeau M, Ko AI, Werling D, Matsui M, Boneca IG, Werts C.

    Front Immunol. 2020 Aug 11;11:2007. doi: 10.3389/fimmu.2020.02007.
     
  2. Alcaraz-López OA, Flores-Villalva S, Cortéz-Hernández O, Vigueras-Meneses G, Carrisoza-Urbina J, Benítez-Guzmán A, Esquivel-Solís H, Werling D, Salguero Bodes FJ, Vordemeier M, Villarreal-Ramos B, Gutiérrez-Pabello JA.

    Transbound Emerg Dis. 2020 Nov 29. doi: 10.1111/tbed.13939.
     
  3. Alcaraz-López OA, Flores-Villalva S, Cortéz-Hernández O, Vigueras-Meneses G, Carrisoza-Urbina J, Benítez-Guzmán A, Esquivel-Solís H, Werling D, Salguero Bodes FJ, Vordemeier M, Villarreal-Ramos B, Gutiérrez-Pabello JA.

    Transbound Emerg Dis. 2020 Nov 29. doi: 10.1111/tbed.13939. 
     
  4. Vander Elst N, Breyne K, Steenbrugge J, Gibson AJ, Smith DGE, Germon P, Werling D, Meyer E.
    Enterobactin Deficiency in a Coliform Mastitis Isolate Decreases Its Fitness in a Murine Model: A Preliminary Host-Pathogen Interaction Study.
    Front Vet Sci. 2020 Nov 9;7:576583. doi: 10.3389/fvets.2020.576583.
     
  5. Holder A, Garty R, Elder C, Mesnard P, Laquerbe C, Bartens MC, Salavati M, Shabbir MZ, Tzelos T, Connelly T, Villarreal-Ramos B, Werling D.

     
  6. Jégouzo SAF, Nelson C, Hardwick T, Wong STA, Lau NKK, Neoh GKE, Castellanos-Rueda R, Huang Z, Mignot B, Hirdaramani A, Howitt A, Frewin K, Shen Z, Fox RJ, Wong R, Ando M, Emony L, Zhu H, Holder A, Werling D, Krishnan N, Robertson BD, Clements A, Taylor ME, Drickamer K.

     
  7. Vats A, Gautam D, Maharana J, Singh Chera J, Kumar S, Rout PK, Werling D, De S. Mol
    Poly I:C stimulation in-vitro as a marker for an antiviral response in different cell types generated from Buffalo (Bubalus bubalis).
    Immunol. 2020 May;121:136-143. doi: 10.1016/j.molimm.2020.03.004.
     
  8. Atashi H, Salavati M, De Koster J, Ehrlich J, Crowe M, Opsomer G; GplusE consortium, Hostens M.

    J Anim Breed Genet. 2020 May;137(3):292-304. doi: 10.1111/jbg.12442. 
     
  9. Jégouzo SAF, Feinberg H, Morrison AG, Holder A, May A, Huang Z, Jiang L, Lasanajak Y, Smith DF, Werling D, Drickamer K, Weis WI, Taylor ME.
    CD23 is a glycan-binding receptor in some mammalian species.
    J Biol Chem. 2019 Oct 11;294(41):14845-14859.
    doi: 10.1074/jbc.RA119.010572
     
  10. Tombácz K, Peters LM, Chang YM, Steele M, Werling D, Gibson AJ.
    Short communication: Pegbovigrastim treatment in vivo does not affect granulocyte ability to migrate to endometrial cells and kill bacteria in vitro in healthy cows.
    J Dairy Sci. 2019 Oct;102(10):9389-9395.  doi: 10.3168/jds.2019-16563.
     
  11. Pilla R, Guard BC, Steiner JM, Gaschen FP, Olson E, Werling D, Allenspach K, Salavati Schmitz S, Suchodolski JS.
    Administration of a Synbiotic Containing Enterococcus faecium Does Not Significantly Alter Fecal Microbiota Richness or Diversity in Dogs With and Without Food-Responsive Chronic Enteropathy.
    Front Vet Sci. 2019 Aug 30;6:277. doi: 10.3389/fvets.2019.00277.
     
  12. García-Sánchez, M; Jiménez-Pelayo, L; Horcajo, P; Regidor-Cerrilo, J; Ólafsson, E B; Bhandage, A K; Barragan, A; Werling, D; Ortega-Mora; L M; Collantes-Fernández, E.
    .
    Frontiers in Immunology, 2019
     
  13. Grelet, C; Vanlierde, A; Hostens, M; Foldager, L; Salavati, M; Ingvartsen, K L; Crowe, M; Sorensen, M T; Froidmont, E; Ferris, C P; Marchitelli, C; Becker, F; Larsen, T; Carter, F; Dehareng, F et al
    .
    Animal, 13;3:649-658. 2019
     
  14. De Koster, J; Salavati, M; Grelet, C; Crowe, M A; Matthews, E; O'Flaherty, R; Opsomer, G; Foldager, L; Hostens, M et al.
    .
    JOURNAL OF DAIRY SCIENCE, 102;3:2631-2644. 2019
     
  15. Tombácz K, Burgess G, Holder A, Werners A, Werling D.
    Toxoplasma gondii profilin does not stimulate an innate immune response through bovine or human TLR5. Innate Immun. 2018 Oct;24(7):422-429. doi: 10.1177/1753425918798450. Epub
    2018 Sep 8. PubMed PMID: 30196747.
     
  16. Dutton LC, Dudhia J, Catchpole B, Hodgkiss-Geere H, Werling D, Connolly DJ.
    Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor. Sci Rep. 2018 Sep 6;8(1):13351. doi:10.1038/s41598-018-31569-1. PubMed PMID: 30190508; PubMed Central PMCID: PMC6127326.
     
  17. Soldevila F, Edwards JC, Graham SP, Stevens LM, Crudgington B, Crooke HR, Werling D, Steinbach F.
    Characterization of the Myeloid Cell Populations' Resident in the Porcine Palatine Tonsil.
    Front Immunol. 2018 Aug 15;9:1800. doi: 10.3389/fimmu.2018.01800. eCollection 2018. PubMed PMID: 30158925; PubMed Central
    PMCID: PMC6104124.
     
  18. Peiravan A, Bertolini F, Rothschild MF, Simpson KW, Jergens AE, Allenspach K, Werling D.
    Genome-wide association studies of inflammatory bowel disease in German shepherd dogs. PLoS One. 2018 Jul 20;13(7):e0200685. doi: 10.1371/journal.pone.0200685. eCollection 2018. PubMed PMID: 30028859; PubMed Central PMCID: PMC6054420.
     
  19. Grierson SS, Werling D, Bidewell C, Williamson S. Characterisation of porcine circovirus type 2 in porcine circovirus disease cases in England and Wales. Vet Rec. 2018 Jan 6;182(1):22. doi: 10.1136/vr.104450. Epub 2017 Oct 19. PubMed PMID: 29051314.
     
  20. Gabai G, Amadori M, Knight CH, Werling D. The immune system is part of a whole-organism regulatory network. Res Vet Sci. 2018 Feb;116:1-3. doi:10.1016/j.rvsc.2017.09.018. Epub 2017 Sep 20. PubMed PMID: 28958409.

 

I am actively involved in both undergraduate and graduate teaching and am happy to hear from potential research students. I have successfully supervised 10 undergraduate research projects, 7 of which were awarded 1sts for their projects. I have successfully supervised 8 (+ 3 current) D.Phil/Ph.D students, all of whom have gone on to successful careers in research and/or industry. Some of my graduate and undergraduate students have won awards and prizes for their dissertations and conference presentations under my supervision.

  • Efficacy testing of novel immersion and oral vaccines for Aeromonas hydrophila in Tilapia and Vietnamese catfish

    Scientists are testing the efficacy of novel vaccines that can be easily administered to farmed fish without the need for highly trained personnel and specialist equipment. Over 30 species are currently farmed, including tilapia and Pangasius (Vietnamese catfish also known as Tra catfish). These fish species are farmed in low and middle-income countries (LMICs) and provide an important source of revenue for many low-income families, supplying both the domestic and export market.

  • Interaction of methanogens with the immune system

    Globally, around 32 percent of global human-induced methane emissions come from livestock, mainly from enteric fermentation and manure management systems. Recent meta-analysis identified that the main intervention to reduce enteric methane production is by direct impacting methanogenic Archaea in the rumen that produce it. Vaccines offer a great potential since they don’t require direct and frequent access to the animals. However, with vaccination, we are faced with diverse problems, the main one being our lack of understanding if and how rumen microorganisms, and more specifically methanogenic archaea, are detected and potentially controlled by the immune system of the animal. The rumen and the large intestine of ruminants are quickly colonized during and after birth by methanogenic archaea and the processes occurring during this colonization over the first weeks of life are critical to understand their recognition by the developing immune system of the animal. This major gap of knowledge needs to be closed before we can fully develop an immunization strategy.

  • LEPTIMMUNHOST

    Leptospirosis is a zoonotic disease due to motile Spirochete bacteria. All vertebrates can be infected with pathogenic Leptospira species, such as Leptospira interrogans (L.i) that is responsible for the more severe forms of disease. Different mammals present various disease symptoms and susceptibility, which is puzzling and not understood. For example, rats and mice are asymptomatic renal carriers of leptospires, cattle suffer morbidity and abortions, whereas humans and hamsters can die from acute leptospirosis. Prevalence of leptospirosis is high in tropical and subtropical areas, and in low-income countries with poor sanitation, where seasonal rains and global warming favor the dissemination of leptospires via contaminated sewage. Despite its health and economic burden, leptospirosis is a reemerging neglected disease, but it is not even cited as such by the WHO.

  • Optimising response to oral yeast-based vaccines against coccidiosis in chickens

    We aim to improve Saccharomyces cerevisiae as an oral vaccine vector platform for use with poultry, focusing on the economically significant disease coccidiosis. We have developed a yeast-delivery platform in which antigens from Eimeria can be expressed in a stable, non-secreted form, with the yeast itself acting as transport system and adjuvant.

  • Protecting Pigs From Enzootic Pneumonia: Rational Design Of Safe Attenuated Vaccines (EPEDC)

    Mycoplasma Hyopneumoniae (M.hyop) is a major worldwide pathogen in the pig industry that is the cause of enzootic pneumonia. Current vaccines are all based on inactivated or subunit approaches but fail to prevent circulation of the pathogen. Evidence from vaccines to other Mycoplasma species, e.g. M.gallisepticum vaccines in chickens suggests that live vaccines can be extremely effective at preventing disease spread. Barriers towards implementation of this type of vaccine for M.hyop include the lack of suitable strains that are sufficiently immunogenic without causing disease. One solution to this problem would be identification genes which contribute towards the pathogenesis of the bacteria as a basis to identify strains suitable to form the basis for new vaccines.

  • SweetAnimals

    The SweetAnimal project studies the presence of sugar-binding receptors in the genomes of a variety of farmed animals, how these differ between species, what ligands expressed on pathogens they bind, and how this information can be used to develop carbohydrate-based vaccines.

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