Q&A: Veterinary Research: Mandy Peffers on osteoarthritis

Mandy Peffers

Although the Wellcome Trust’s mission is to foster and promote biomedical research, its mission encompasses both human and animal health.

The Trust supports a range of activities designed to encourage veterinarians to take up research careers. Many of its fellowships, at all levels, are open to veterinary-trained researchers, and there are also three dedicated fellowship schemes for veterinary graduates and postdoctoral researchers.

Mandy Peffers from the University of Liverpool holds a Wellcome Trust Integrated Training Fellowship for Veterinarians, a programme that provides funding for a PhD and further clinical training over six years. In the last of three articles focusing on the veterinary fellows, Ailbhe Goodbody speaks to her about her research.

Why did you choose to study veterinary science?

I didn’t get the A-levels to do Veterinary Medicine, so I did Animal Science at the University of Leeds instead. Once I had finished that I applied for PhDs, and was offered a few of them, but I also applied to the Royal Veterinary College and was offered a place to go straight into second year. I decided that I should do the veterinary course, and that I could always do a PhD afterwards. However, I ended up spending ten years working in industry and am only doing the PhD now, which is really thanks to the Wellcome Trust veterinary research initiatives.

What is it that attracted you to the research aspect of veterinary science?

I have always been interested in finding out the reasons why things happen, rather than just learning facts and regurgitating them for exams. When I did my first degree, one of the things I enjoyed the most about studying science was finding out things for myself and doing research projects. As part of my veterinary degree, I did a dissertation that involved research and I found that really interesting as well. There are so many questions that people are trying to answer but that they haven’t got to the bottom of yet – what are the reasons behind these diseases? I suppose that is what attracted me to go into research.

I decided on a field that I was interested in, and I went to talk to a supervisor I knew from my veterinary degree. It turned out that he was the Dean of Research at Liverpool. I was quite proactive – I didn’t wait for it to come to me, I sought out what I wanted to do. Also, I have been really lucky to get funding from the Wellcome Trust, which has helped me enormously.

When did you get the fellowship?

Since I had been out of university for a while, I was advised to do the one-year Wellcome Trust Veterinary Research Entry Fellowship first, which is for people who are interested in going into veterinary research. It was very successful, and as a result I successfully applied for the Integrated Training Fellowship for Veterinarians. The first three years of funding are for a PhD – I just started my second year in November – and then I have three years of funding for clinical training, and will be able to apply for a European Veterinary Diploma in the area I study, which in my case is diagnostic imaging.

What does your research focus on?

My research focuses on osteoarthritis in humans and horses. Horses, because it is easier to get the samples for our models, and humans, because although most research is done in animal models, it is ultimately geared towards human treatment. We use both systems in the research I’m doing at the moment.

What exactly is it that you’re investigating?

Cartilage is made out of a specific cell type called a chondrocyte, and the rest of it is extracellular matrix. In osteoarthritis there is a breakdown in that matrix, and the first constituent part that breaks down to is a protein called aggrecan. There is a destruction of aggrecan core protein by protease enzymes, which generates a complex pattern of fragments. We want to measure the degradation products of the proteases to find out if there is a specific sequence in which the aggrecan molecule is broken down, and hopefully quantify it as well.

We’re looking to develop a QconCAT, which is an artificial protein made up of a mixture of tryptic peptides for several proteins that one is interested in absolutely quantifying. You can put it into your sample to help work out the concentration of the protein you want to look at using mass spectrometry.

And this work can be applied to horses as well as to humans?

Just after my first year I developed a QconCAT for specific proteins in the cartilage secrotome (collection of secreted proteins), and that was for humans. However, some of the protein sequences that I study are the same in humans and in horses, so I can just apply the same QconCAT to horses. It is much easier to get horse samples of different ages to look at – the ethics for human samples is much more complicated. We do have ethical approval for human samples in our group, but we commonly have more access to diseased cartilage from total knee arthroplasty operations than from normal joints, which are derived from amputations.

Horses are not necessarily more prone to osteoarthritis than any other species; we are probably seeing it more now because the age of the horse population here is increasing. It’s the same in dogs – a lot of dogs are treated symptomatically for arthritis.

I think that vets can contribute to other fields. We have a different way of looking at diseases, so veterinary research will have beneficial effects for both the human and animal populations.

Why did you choose this area of research?

In veterinary medicine, a lot of the diseases you deal with now are age-related diseases, and osteoarthritis is one of the big ones. There are currently few scientifically proven preventative treatments for osteoarthritis; all the treatments are primarily aimed at pain relief. Occasionally hip joints can be replaced. As a result, it is a big area of research, but it’s also quite an exciting area as there is potential for great discoveries.

I’m the only one in the proteomics group doing research into osteoarthritis. The mass spectrometry we use would be quite a new approach for the study of osteoarthritis. Every year the technology for the machines gets better, making them more sensitive and increasing the amount of data we can get from the samples. It is exciting, because the field is moving along so quickly.

Why don’t more vets go into veterinary research?

Veterinary research isn’t particularly well funded, especially in the current economic climate, but I don’t think that this is necessarily what stops people from going into research. It is more that people go into veterinary science to become a vet, and they don’t think about any options other than going into veterinary practice and becoming what they see as a normal, James Herriot type vet.

Initiatives such as those run by the Wellcome Trust, where people go into the universities and talk about vacation studentships, summer schools and other opportunities, make veterinary students aware that there are more options than going into practice.

I have talked to some of the students in the University of Liverpool about intercalating, which gives them the option of doing more research than in a normal veterinary degree. I also tell them about my experience with the Wellcome Trust fellowships, about what you can do, so that they’re aware that the funding is there if they want to apply for it. I think that it is the best thing I have ever done. I really enjoy it – the challenge, the people, and the environment. I can’t think of anything else I would prefer to do!

Find out more about the Wellcome Trust’s Veterinary Research Fellowships.

Ailbhe Goodbody