Dr Sara Clohisey on patient genetics in acute illnesses

How DNA affects illness, disease life cycles and the motivation of caring for others.

Dr Sara Clohisey is a Core Scientist in the Baillie Group at the Roslin Institute, where she studies molecular interactions between viruses and white blood cells in humans. In this interview, she talks to MSc Science Communication student Elise Cutforth about her research, expanding a clinical trial to cope with Covid-19, and working in a patient-centric field of science.

What’s your background?

I grew up in Dublin, in Ireland, and did my undergraduate degree there in biochemistry and cell biology, before moving to the University of Edinburgh to work on my PhD. I usually describe my PhD as looking at cancer in fruit flies, but it was more to do with the cytoskeleton – a network of fibres inside cells – and a protein associated with cancer in humans. It was very cell biology-focused and after that I wanted a bit of change, so I came to Roslin, where we focus on how the genetics of a person or animal can affect their experience of acute illness or critical care.

Why did you become a scientist?

I’ve always been curious, which I think is the stock answer. I’ve always been interested in asking questions about everything and when it came to my career I followed the fun. Science was always what I enjoyed the most at school so when it came to choosing a university course, it seemed a no-brainer. Prior to moving to Edinburgh, I was a home carer and so I had a lot of one-on-one interaction with people who were very ill and I wanted to be able to do something that would eventually be helpful, so that definitely encouraged me.

What does a typical work day look like?

My main focus before the pandemic was in looking at the molecular interaction between the flu virus and white blood cells in humans, using a method called cap analysis of gene expression (CAGE) to look at genetic material called RNA.

Flu doesn’t have its own machinery to replicate, it actually steals a lot from the infected cell. When it does this, it incorporates a molecule used in the initiation of DNA synthesis into its RNA, stolen directly from the host’s RNA. So if you have flu, every single flu RNA has a little bit of you in it. I use CAGE to look at those and to analyse them in comparison to the same sequences in the background population of RNA in the host. We were able to determine which RNAs were bring targeted by flu, which was really interesting.

A typical day may involve analysing data on a computer or experiments involving infections in white blood cells, which can involve getting a blood sample. I’m doing very similar work now, with SARS-CoV-2. So earlier this week I added SARS-CoV-2 to some blood cells, to see how they would respond to the virus.

How has Covid-19 affected your work?

We have had to massively scale-up our clinical study, which collects blood samples from people who are in critical care, extracts the DNA and decodes its sequence. We are looking for genes associated with inherited susceptibility to specific diseases, and that includes infection with SARS-CoV-2.

At the outset of our study in 2016, we were hoping for 6,500 samples within 10 years, but just four years on, due to the pandemic, we are at 12,000. At the beginning of lockdown we had more than 70 volunteers helping us to prepare boxes being sent out to collect samples, and we have since had to outsource this. We have had to expand and collaborate with other labs at the University to be able to adapt to this much larger scale and, as a result, we have been able to analyse and release our data quickly, so others can use it too.

What challenges do you face as a scientist?

I think the main challenge at the moment is the funding issues. We have seen cuts already to funding and it seems like there are more on the way. Anyone who is trying to work full-time in a lab is going to be anxious when we are told there might not be enough funding to prolong contracts. Particularly after this year, when people may reach the end of their contract without any outputs they can show in the job market, it’s going to be a major challenge.

Do you participate in science communication?

I’ve recently taken part in the ‘Meet a Roslin Scientist’ initiative for schools, which was really exciting because I got to talk about my Covid-19 related work. We got some very delicate questions from the kids, who were genuinely scared, and it was very eye-opening to see just how mature they were in asking their questions.

Apart from that, in the lab I work in, we interact a lot with the Fiona Elizabeth Agnew Trust (FEAT) which is a sepsis charity. We often host individuals who are involved in the charity, showing them what we do and how long it’s going to take, and it’s incredible to meet people who our research is directly affecting.

As I have progressed through my career into a more translational field of science, my outlook has changed slightly. Working in a more patient-centric side of science, I feel there is more of a responsibility to carefully communicate how the science works.

What do you see for the future of your research?

In my lab, we envision a situation where we can identify specific changes in a person’s DNA that lead to a difference in their response to disease. By identifying those changes we can find points within the biomolecular pathways that we can target with drugs, potentially by repurposing existing drugs. This would give us a point to intervene and improve the outcome, instead of just stabilising someone when they’re in critical care. Our research is currently being used in recovery clinical trials for Covid-19 and in the future we hope to achieve this for flu and sepsis.

If you weren’t a scientist what would you be doing?

If I wasn’t a scientist I would probably be doing something in home care. As I said, during my undergraduate degree I was a home carer, and I like looking after people and making people’s lives easier, so I think that’s probably what I would’ve gone into.