Professor in Reproductive Immuno-Biology
Biomedical Sciences
Telephone: (01792) 602709
Room: Academic Office - 429
Fourth Floor
Institute of Life Science 1
Singleton Campus

Professor of Infection and Immunity

Biography

I qualified as a veterinary surgeon (BVSc, MRCVS) in 1984 and worked in clinical practice for 14 years in Wales. Whilst in practice I studied for two clinical Diplomas (DBR, DCHP), and then started work on a PhD supervised by Prof Hilary Dobson at the University of Liverpool. In 1998 I moved to the Royal Veterinary College in London, and I was awarded my PhD by Liverpool University in 2002. In 2006 I was awarded a BBSRC Research Development Fellowship to further my interests in host-pathogen interactions. In 2008 I was appointed to a Personal Chair in Infection and Immunity at Swansea University Medical School. In 2013, I was awarded FRCVS for meritorious contributions to research, and in 2015 I was awarded the Schofield Prize.

Research Interests

My group study the mechanisms of interactions between hosts and pathogens. We are interested in how bacteria cause disease. On the other hand, we also aim to understand how animals and humans defend themselves against infections and prevent disease by avoiding, tolerating and resisting pathogenic bacteria.

During my PhD I discovered that the function of the ovary is perturbed in animals with uterine bacterial infections. Our first research question was what protects oocytes in the ovary from damage caused by these bacterial infections? We initially worked how microbes cause inflammation and tissue damage in the endometrium of the uterus, and how this affects the ovary and the oocyte. Key discoveries were that the epithelial and stromal cells of the endometrium, and the granulosa cells of the ovary have roles in innate immunity. In particular these cells express receptors, such as Toll-like Receptors (TLRs), which detect pathogen-associated molecular patterns to induce inflammatory responses, including the production of cytokines, chemokines and prostaglandins. Furthermore, pathogen-associated molecules perturb oocyte health and development, linking bacterial infections to long-term impacts on fertility.

Pore-forming toxins are the most common virulence factor used by bacteria to damage host cells, which leads to tissue pathology. Our second research question is how do cells protect themselves against pore-forming toxins? We have focussed on cholesterol-dependent cytolysins, as these are the most common pore-forming toxin. We study the cellular responses to pore-forming toxins., and the molecular mechanisms of cytoprotection against pore-forming toxins in tissue cells. Increasing the protection of cells against bacterial virulence factors is an alternative to using antimicrobials to kill bacteria, helping in the fight against antimicrobial resistance.

Areas of Expertise

  • Host-pathogen biology
  • Innate immunity
  • Reproductive Biology

Publications

  1. Sheldon, M. Preventing Postpartum Uterine Disease in Dairy Cattle Depends on Avoiding, Tolerating and Resisting Pathogenic Bacteria Preprints 2019080140
  2. Raliou, M., Dembélé, D., Düvel, A., Bolifraud, P., Aubert, J., Mary-Huard, T., Rocha, D., Piumi, F., Mockly, S., Heppelmann, M., Dieuzy-Labaye, I., Zieger, P., G. E. Smith, D., Schuberth, H., Sheldon, I., Sandra, O., Sheldon, M. Subclinical endometritis in dairy cattle is associated with distinct mRNA expression patterns in blood and endometrium PLOS ONE 14 8 e0220244
  3. Turner, M., Owens, S., Sheldon, M. Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria bioRxiv 10.1101/679068
  4. Piersanti, R., Horlock, A., Block, J., Santos, J., Sheldon, I., Bromfield, J., Sheldon, M. Persistent effects on bovine granulosa cell transcriptome after resolution of uterine disease Reproduction 158 1 35 46
  5. Carvalho, A., Eozenou, C., Richard, C., Forde, N., Healey, G., Giraud-Delville, C., Mansouri-Attia, N., Lonergan, P., Sheldon, I., Sandra, O., Healey, G., Sheldon, M. Bovine scavenger receptor class A (SR-A) exhibit specific patterns of regulation in the endometrium during the oestrous cycle and early pregnancy Reproduction, Fertility and Development
  6. Sheldon, I., Cronin, J., Bromfield, J., Sheldon, M. Tolerance and Innate Immunity Shape the Development of Postpartum Uterine Disease and the Impact of Endometritis in Dairy Cattle Annual Review of Animal Biosciences 7 361 384
  7. Sheldon, I., Sheldon, M. The Metritis Complex in Cattle (Ed.), Veterinary Reproduction and Obstetrics 408 433 Elsevier
  8. Piersanti, R., Zimpel, R., Molinari, P., Dickson, M., Ma, Z., Jeong, K., Santos, J., Sheldon, I., Bromfield, J., Sheldon, M. A model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes Journal of Dairy Science 102 3 2686 2697
  9. Sheldon, M. Metabolic stress and endometritis in dairy cattle Veterinary Record 183 4 124 125
  10. Britt, J., Cushman, R., Dechow, C., Dobson, H., Humblot, P., Hutjens, M., Jones, G., Ruegg, P., Sheldon, I., Stevenson, J., Sheldon, M. Invited review: Learning from the future—A vision for dairy farms and cows in 2067 Journal of Dairy Science 101 5 3722 3741

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Teaching

  • PM-249 Human Immunology

    The course is designed as an introduction to immunology and the human immune system. The course covers the fundamentals of immunology including functional perturbations associated with disease and experimental approaches to the study of immunology.

  • PM-304 Biomolecular Research Project

    *

  • PM-344 Capstone Project

    The aim of this module is to provide a capstone experience to students¿ learning, through participating in their own enquiry-based research project. Depending on the student's employability strand within the programme, the project may be laboratory, data, or education-based, but it will always involve a research question that is drawn from the literature, focused on a topic relevant to medical science. It will ask a novel research question and involve the critical analysis of research findings. Students will refine their oral and written communication skills to a graduate level through creating an introductory presentation on the project background, and a written dissertation and oral presentation on their research conclusions.

  • PM-347 Human Immunopathology

    The module aims to provide students with a greater understanding of the human immune system and the causes of a range of diseases associated with immune dysfunction including autoimmune diseases, metabolic disorders and neurological conditions.

  • PM-352 Reproductive Biology and Medicine

    This module is designed to provide students with knowledge of the biochemistry, physiology and pathology of human pregnancy, fetal development, parturition and menopause. Particular focus will be given to fertility treatments and pharmacological interventions of menopause. Lectures will cover a recap of endocrinology of reproduction, and provide details of assisted reproductive technologies. Lectures will be supported by case studies which include current clinical approaches used to treat infertility and menopause.

  • PM-401 Science Communication

    This module will encompass a range of communication modes, from presentation of science to the general public to making a pitch for funding to `investors¿ The module will be run as a series of online seminars to prepare, firstly, for a short 3 minute thesis-like presentations to both a professional and non-professional audience. This will be complemented by preparation of short, New Scientist-style articles by each student on the topic of their presentation. Students will be assigned a topic that is appropriate to their degree title. For example, a Medical Geneticist could address recent advances in gene therapy. Subsequently, their task will be to produce a pitch to attract investment to commercialise their research. In the latter half of the module, the focus will be on skills-training for writing a scientific paper, preparing the ground for their project dissertations.

  • PMLM06 LC/MS Applications V: Metabolomics, Lipidomics and Bioactive lipids

    This module covers the basic concepts of metabolomics, lipidomics and analysis of bioactive lipids. The module will focus on the application of LC-MS analysis of biomolecules isolated from complex mixtures.

Supervision

  • Bisphosphonate inhibitors of squalene synthase protect human tissue cells against cholesterol dependent cytolysins from pathogenic bacteria (current)

    Student name:
    PhD
    Other supervisor: Dr James Cronin
    Other supervisor: Prof Martin Sheldon
  • Cellular regulation of protection against cholesterol-dependent cytolysins by steroids and oxysterols (current)

    Student name:
    PhD
    Other supervisor: Dr James Cronin
    Other supervisor: Prof Martin Sheldon
  • Role of Mitochondrial pyruvate carrier in ovarian cancer progression (current)

    Student name:
    PhD
    Other supervisor: Prof Martin Sheldon
    Other supervisor: Prof Deyarina Gonzalez
    Other supervisor: Dr James Cronin
  • Mechanisms of Mammalian Egg Resilience, from the Macro to the Nano scale (current)

    Student name:
    PhD
    Other supervisor: Dr Martin Clift
    Other supervisor: Prof Martin Sheldon
  • The role of cysteine desulfurase (NFS1) in iron nanoparticle-induced ferroptotic cancer cell death (current)

    Student name:
    PhD
    Other supervisor: Dr James Cronin
    Other supervisor: Prof Martin Sheldon
  • Targeting Therapy-Resistant Ovarian Cancer by Induction of Ferroptotic Cell Death (awarded 2019)

    Student name:
    MSc
    Other supervisor: Prof Martin Sheldon
    Other supervisor: Dr James Cronin
  • 'The host-pathogen interactions between Trueperella pyogenes and the endometrium' (awarded 2017)

    Student name:
    PhD
    Other supervisor: Prof Martin Sheldon