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MEET OUR PHD RESEARCHER!

PhD candidate Dearbhla Murphy is in the second year of her PhD studies in the school of Medicine, and is studying how our immune system interacts with Mycobacterium tuberculosis (Mtb), the bacteria that causes tuberculosis (TB). Dearbhla first studied Immunology in Trinity College Dublin and then worked as a Research Assistant for Dr Frederick Sheedy, an Ussher Assistant Professor in Biochemistry. Whilst working with Dr Sheedy, Dearbhla first became interested in TB. She then went on to work with Professor Derek Doherty (Professor of Immunology and Head of Immunology) on culturing different types of T cells for cancer immunotherapy, and eventually worked on a side project involving TB. Therefore, she was delighted when an opportunity came up to study alongside Dr Sharee Basdeo, a Research Assistant Professor in Clinical Medicine.

In the past few years there has been a rise in the number of drug-resistant TB cases, meaning the current drugs we have to fight TB do not work against the bacteria. Host-directed therapies aim to boost a patient’s own immune response to help eliminate the bacteria in conjunction with antibiotics. In 2019, 53,000 cases of TB were reported in Europe, with 267 of those cases occurring in Ireland. Increasing cases of drug resistant TB are a global threat to public health. Dearbhla is interested in how both our innate and adaptive immune system fights Mtb and how that might be used to our advantage. She has already won prizes for her research - including the 2021 Faculty of Health Sciences Thesis in Three Competition (runner up prize) and a best poster presentation award at the European Congress of Immunology Conference (2021). Recently, we spoke to Dearbhla about her PhD studies and her plans for the future.

People may regard TB as a disease of the past, but it is still very much a current issue. Could you explain the gravity of the problem?

Yes, when it comes to TB, people think of the word ‘consumption’ and of sanitoriums and the late 19th century. However, TB is very much a current scourge; it is currently the second leading cause of death from an infectious agent after COVID-19 and the 13th leading cause of death worldwide. It was also the leading killer of people with HIV/AIDS. Further to this, TB is a major contributor to deaths from antimicrobial resistance. In 2020, there was 10 million reported cases of TB, and 1.5 million people died from TB. Of these 10 million cases, about half a million are drug resistant. Many people suffering with the drug resistant TB do not reside in countries with the infrastructure or resources to treat it. It’s estimated that only one in three people with multi-drug resistant TB receive the necessary treatment to alleviate it, which is a great inequality as well as a public health concern.

Describe how your PhD studies aim to tackle this condition.

I am interested in using a form of immune ‘training’ which boosts our innate immune system, improving its ability to eliminate Mtb right after exposure to the bacteria, before it causes disease. TB is a very complex disease, where the immune response acts like a double-edged sword – too little inflammation means you won’t eliminate the bacteria but too much inflammation results in damage to the lungs. As such, I am also interested in better understanding the bidirectional interactions between these early ‘trained’ innate immune responses and longer-term immune responses with the aim that this work may inform the design of new host-directed therapies and vaccines against TB.

How do you see your work impacting public health?

I hope that my work will have the potential to form new host-directed therapies or vaccine design, not only for TB but for other emerging infections and drug-resistant infections, with an end goal of eliminating these infections. In addition to this, better understanding of the fundamentals of the human immune response will also inform diverse areas of medicine that are impacted by altered immune function, such as cancer and autoimmune diseases.

Did you always want to pursue this type of career?

No, when I was at school, I wanted to study English and History and become a teacher. It wasn’t until I was in my sixth year of school that I realised that I loved biology and learning about how our bodies work. I had never considered a career in science because I didn’t know what it entailed, and I was worried that I wasn’t going to be clever enough to work in research. However, once I got to college, I worked hard, and I found myself loving science more every day. I knew I wanted to do a PhD when I was in my third year of college and from then on, I tried really hard to make that happen.

I am now lucky to work with a lot of wonderful and inspiring people, including my PI Dr Sharee Basdeo, my lab mate Sarah Connolly, and I get invaluable support from Professor Joseph Keane’s Immunology Group, and in particular Dr Donal Cox and Dr James Phelan.

Do you recommend the PhD or academic life to young students and undergraduates?

I love working in research. I love problem solving and I love the idea that the work I’m carrying out could help someone in the future. Doing a PhD is hard, there are times when everything goes wrong and you can lose motivation, but it’s never boring – every day is so different - and it’s so exciting when the experiments start to work and you realise that you’re on to something!

If you’re interested in pursuing a PhD, I would highly recommend it. I find a lot of motivation in the thought that the work I’m carrying out now, in a big or a little way, could directly or indirectly add to our understanding of how we work and how we can make our immune system work better to protect us from disease. TB research also has a special place in my heart as it’s a problem that primarily exists in the developing world and deserves more research focus in the west.

What are your plans for the future?

I would love to continue working in research. I’m very passionate about immunology and I would love to continue to explore how our bodies fight infection and how we can help people who become sick with these diseases, especially those in the developing world who do not have access to the medicine and resources we do. I think the best way we can hope to combat microbial resistance and infectious disease is through vaccine design. The COVID-19 pandemic really highlighted the importance of vaccines in fighting infection and the need for developing innovative new ways to vaccinate against elusive microbes. It also highlighted the importance of investing in this inventive work. I hope I might be able to contribute something to that work in the future.

When you are not working on your PhD studies, where could we find you?

I love movies and going to the cinema, it’s probably my favourite way to relax and disengage with the outside world for a bit. I also fell back in love with baking during COVID and I love to bake at the weekends to burn off some steam.

To read some of Dearbhla’s published work, click here: https://www.frontiersin.org/articles/10.3389/fimmu.2021.706583/full?&field=&journalName=Frontiers_in_Immunology&id=706583