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Dr Mark Gray on large animal models of disease

Dr Mark Gray is a veterinary surgeon who applies his expertise to develop and study large animal disease models. He tells us about his career path, the benefits of working in a novel area, and making a contribution to One Health research.

How would you describe your work in a nutshell?

My work focuses on the development of large animal models, not only for studying veterinary diseases, but also to improve research into human health. I see myself as carrying out One Health research through investigating animal diseases and the translational aspects of applying this research to human health. Historically, small animal rodent models have dominated preclinical research; while these models can be great for studying the molecular basis of diseases, due to their size they cannot be used effectively as a translational surgical model for human procedures. Depending on what you're trying to do, pig or sheep models can be much more relatable to a human procedure.

For example, my particular interest and research involves Ovine Pulmonary Adenocarcinoma (OPA), which is an infectious, fatal lung cancer that affects sheep. This disease is common throughout the world and causes serious economic and animal welfare issues. My research aims to better understand the pathogenesis of the disease and to develop new diagnostic tests to improve disease control. The disease also shares histological characteristics with certain forms of human lung cancer; as the lungs of people and sheep are similar in size, physiology, and shape, we are pioneering the use of OPA as a model to validate novel human cancer therapeutic strategies.  

I divide my time broadly between surgical work at the campus’s Large Animal Research and Imaging Facility (LARIF), working on my own research, and teaching surgery to veterinary students. I have an unusual role on campus in that I split my time between these areas. Besides teaching, I work with students on extracurricular studies, and as a mentor. It’s different from my other responsibilities, and I enjoy it. I want to do my best by them, especially when the exams come around and they're all feeling stressed.

Can you summarise your background and career path?

I'm from a farming background in East Yorkshire in the North of England, and I always had an interest in farm animals. I remember as a boy bringing our small herd of sheep into the shed for lambing, sitting on bales of hay, with the lambs jumping about.

I came to the University of Edinburgh to do my veterinary degree, then I went to work in mixed animal veterinary practice, before moving to the People’s Dispensary for Sick Animals as a small animal vet. Then I took surgical exams and did a masters, again at Edinburgh, in oncology with regards to investigating feline mouth cancers. After that, I worked as an orthopaedic surgeon in Fife, before returning again to Edinburgh for a PhD in oncology. During my PhD I developed animal models that could be used to research oxygen-sensing implants for monitoring and treating tumours. This was the start of my work in sheep lung cancer. Following my PhD and a short period as a research assistant at the University, I became a Lecturer and then finally a Senior Lecturer in Large Animal Surgery at the Vet School in 2020.

What are the main projects you’re focused on?

The main project I run is all to do with understanding OPA for veterinary and human health related activities. However, I still collaborate with my colleagues in the School of Engineering, who I worked with on my PhD on the oxygen sensors research. We are interested in developing this for monitoring oxygen levels in the human intestine, during healing after surgery. I also contribute to other projects where a surgical component is involved in the LARIF, for example in research into tuberculosis in cows, and investigations into glioblastoma and a form of childhood dementia using a sheep model.

What do you enjoy about your work?

I don't think I could do my research-based veterinary surgery work anywhere else but here at Roslin. Because of the facilities that we have available here, I think this is probably the best place to be doing my type of research. I was of course familiar with the Roslin Institute before I came to work here, and knew a network of people, having done my veterinary degree across the road in the Vet School. I enjoy the stimulation of working with other people, such as planning an experiment with someone, talking it through and finding the best way of doing something. We each bring different skills to the table, but we're all on the same page.

I enjoy trying to do something new or researching something novel, such as defining the boundaries of what an animal model can do, or what we can use it for. With the OPA work, we’re uncovering new veterinary aspects such as how infectious the disease is and how fast the tumours grow, and why some of the sheep don't develop tumours or have susceptibility to developing the disease.

With the model, we've shown that most of the sheep exposed to the virus do get infected, but a lot of them don't develop tumours; there must be a reason why – and that's relatable to what's happening in a farmer's flock. Ultimately, I want to advance OPA research, and I want to make a blood-based diagnostic test for it. I hope we can use our model to enhance the control of OPA, by deepening our understanding of the infectious nature of the disease and improve sheep welfare.

What do you find challenging?

Applying for funding is always challenging; you have to keep putting in applications, take on reviewers’ comments and keep going. There can be a lot of paperwork to manage, for example in finance or in organising contracts associated with a project – I haven't got that background or experience and I rely on our in-house experts.  Some challenges I enjoy, such as learning a new surgical procedure – perhaps with surgical principles that are familiar, but with a different nuance. I’ve learned novel procedures that not many people are using. I've learned a lot about CT imaging and CT scanners too.

If you weren't doing research-focused veterinary surgery, what would you be doing?

I think I might enjoy being a farmer. I always enjoyed being on the farm as a child. I can see the advantages of being in a field all day on my own, ploughing away. I could see myself doing that, in a nice little farmhouse somewhere with a Nissan GTR Nismo on the driveway. It would be hard work, but I don't mind long days and working hard. I‘d have some sheep and Highland cows for company.