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Dr James Prendergast on genetics of disease resistant cattle

The challenges of collecting data, enjoying job satisfaction, and finding inspiration in others.

James Prendergast

Dr James Prendergast is a group leader at the Roslin Institute whose work focuses on understanding mammalian gene regulation, genome evolution and human and animal disease genetics. In this interview he talks to MSc Science Communication student Clemency Magan about his research.

Could you tell me about your research in a nutshell?

I’m a bioinformatician – we spend our whole time behind a computer, collecting, studying and analysing data. In our lab we are interested in humans and in livestock and comparisons in terms of how their genes affect disease. The core of what we do is looking at how regions of DNA that give rise to particular traits may be affecting both humans and cattle.

What brought you into science and into this field of research?

My undergraduate degree was in molecular biology at the University of Edinburgh, followed by a masters in bioinformatics at Glasgow. To be honest I didn’t know what to do after my masters and applied for a PhD in bioinformatics and statistical genetics, for which the details had been emailed to our bioinformatics course. Fortunately, in my PhD I was involved in one of the first large genome-wide association studies of colorectal cancer, trying to map the genes linked to increased risk of the disease, which was really enjoyable. After my PhD I had short positions in Cambridge and Dublin then left science, but missed it and returned to Edinburgh and the Institute for Genetics and Molecular Medicine. A few years ago I moved to Roslin.

One of the great things about science is there is a lot of freedom to do what you want – if there a question that’s interesting, you can go after it. That’s what attracts me to working in science.

What are the real-world applications of your research?

We are hoping to exploit one of the findings from one of our cattle studies. East Coast fever, a tick-borne disease common in Africa, can result in US$400 million of losses to farmers each year. Within the Centre for Tropical Livestock Genetics and Health (CTLGH) we’ve been collaborating with the International Livestock Research Institute in Kenya to try to understand why some cattle appear tolerant to the disease. We have mapped a potential region of DNA which makes some animals naturally tolerant to infection. In areas that have high levels of disease the animals carrying this bit of DNA will still get sick, but they normally pull through compared with a lot of other breeds, especially European ones. The hope is to introduce this genetic change into European breeds, which may be more productive but are generally less resistant to disease.

Has the technology changed a lot in your field over the years?

Certainly in genome sequencing, it’s so cheap now. It makes bioinformatics a lot easier. When I started the human genome had just been published and it cost over US$1 billion. I just got a quote for a new genome that costs US$3000 now, to generate a genome largely as good as the original.

What would you say to a young person thinking of going into research or science?

I would certainly encourage it. With the current pandemic situation, scientists are doing better than at any other time, and that’s a good thing. Science has the opportunity to do lots of good things - not just Covid-related research but also cancer and other diseases. There are not many jobs that you can get that kind of satisfaction, where you feel what you’re doing is interesting - there are journal papers I’ve authored that will be there after I’m gone.

Do you think science communication activity has increased?

I think so, yes. I don’t remember it coming up during my PhD and no one really did it then. But now PhD students definitely have lots of opportunities to get involved, especially at Roslin, as they are well equipped with the campus Science Outreach Centre too.

In the future is there a particular project you would like to undertake?

We are looking into graph genomes. At the moment we only have one reference genome for one animal, and we’re trying to generate lots of genomes for lots of breeds, which would make the results much more representative of the species. African cattle are massively under-represented, for example, in a lot of our resources.

The same issue is true in humans, a lot of the data generated around the human genome is for European or Western countries, and Africa and Asia are massively under-represented. That makes studying diseases relevant to these populations more difficult.

What challenges in the field could be helped by technology?

For research in Africa, it’s difficult getting there and obtaining samples. Fortunately, I have collaborated with a lot of great people here and in Africa. Collecting data is difficult, analysing it is the easy bit!

We can map which regions of the genome are associated with increasing the risk of cancer in humans or milk production in cattle. But for the vast majority, we don’t know what the actual genetic variation is in the region that confers the difference.

It’s a big challenge trying to bridge that gap. We know all these regions that are associated with diseases and traits. If we don’t know what the variants are, though, it’s very hard to act on them in terms of their biological pathways, for example in drug targeting, or to use genome editing to introduce the same effect into other breeds.

Who would you like to have tea with and why?

Tuuli Lappalainen, a leading geneticist, was in charge of the Genotype Tissue Expression (GTEx) project, which produced a resource of information on regulatory variants in humans. It’s an amazing dataset that my colleagues and I have spent time working with. All her papers are great, I’d like to chat to her.

What would you be if you weren’t a scientist?

I tried to be an airline pilot and was asked back for a second interview but decided against it. I was deep in my research at that point and decided doing science would probably be more enjoyable.

Related links

Centre for Tropical Livestock Genetics and Health

Researcher honoured for work on cattle disease