26 Jul 2023
Q&A with Virus Cell Biologist: Clare Jolly, UCL
We speak with WellcomeTrust Investigator Professor Clare Jolly in the lead up to her research seminar at the Department of Microbiology and Immunology on Thursday, 3 August.
As a Professor of Virus Cell Biology at University College London, Clare's research is focused on the viral and host processes that occur during viral infections. In particular the cellular and molecular processes regulating HIV-1 infection and its spread between T cells, the white blood cells that play a critical role in the immune system.
Her current work is looking to understand what makes a T cell susceptible to HIV-1 infection and how the virus reprograms T cells to to cause disease and evade the host's immune system and defences.
"My research group is also working on SARS-CoV-2 virus-host interactions and looking at innate immunity - the body's first line of defence - and VOCs and how they have evolved to evade human innate immune sensing and antiviral restriction."
Clare did her undergraduate degree at the University of Melbourne. She went on to do her honours project with Professor Ian Holmes in the Department of Microbiology and Immunology mapping antibody epitopes on rotavirus antigenic proteins, followed by her PhD in the same research group, focused on rotavirus.
Here's what she had to say about her time at Melbourne - and her pathway to where she is now.
Can you tell us about some of your key achievements and projects when you were studying at the University of Melbourne?
The Department of Microbiology and Immunology was an excellent environment to start out my scientific career. I was surrounded by outstanding scientists and there was a real sense of community. As a student, we were very fortunate that there was a very positive research culture and interaction between students, staff and the Group Leaders.
Looking back, I think it is rare to have an environment where students felt they could approach Group Leaders and senior postdocs from other labs, and I think that was tremendously beneficial and I learnt a lot from my time there - not just how to do science but how to create an environment where science and training can flourish.
What skills and experience did you gain from studying at the School of Biomedical Sciences?
I learnt how to think scientifically, and how to plan and execute an experiments independently, how to write my own papers, how to present my work at lab meetings and conferences. I guess you can sum it up as: "I learnt how to become a scientist". I published 4 papers, 3 as first author from my PhD.
You worked with Ian Holmes who discovered rotavirus which is a huge legacy for the Dept of Microbiology and Immunology – what can you recall about your time with him?
Ian was a very well respected - I once heard him referred to as a “gentleman scientist” and that is certainly how I remember him - he never had a bad word to say about others, either professionally or personally.
What I learnt most was how to be independent, Ian gave us freedom to pursue our own ideas, and that is a rare thing nowadays. The pressure to publish and “be first” means that there is a lot more “helicopter” supervision but I was very fortunate to get the opportunity to learn how to plan my work, try things out and do discovery science. Ian was very supportive of my plans for a postdoc overseas and that was very helpful at that stage in my career, to get that support and encouragement.
It is a rare experience to get to work with someone who discovered the virus you are working on.
You went from ICL to Oxford after your PhD, and then on to your current appointment at UCL – what can you share with us about these experiences?
Imperial College London
I went from my PhD to Imperial College London for my first postdoc in the lab of Professor Quentin Sattentau. I had been awarded a Wellcome Trust Travelling Fellowship that funded my postdoc salary to work on HIV and mechanisms of viral spread between T cells.
This was a hugely formative time. Quentin was a fantastic supervisor, he is a really positive person and was a great mentor and I was introduced to lots of people in the HIV field. Imperial College had a large number of world-leading virology labs and it was an exciting place to do science. The quality of the research was outstanding and it was next level, and I learnt a lot interacting with the people in those labs.
I did the work that has shaped my career, I published a first author paper in Quentin’s lab in the Journal of Experimental Medicine (JEM) where we discovered how HIV spreads between T cells by a process of cell-cell spread at a structure we termed the virological synapse. This work was a paradigm shift in understanding the mechanism of HIV spread between immune cells - and has been a focus of my research since.
I was in the thick of HIV research in London and then Oxford, surrounded by amazing scientists and getting to regularly go to international conferences, and meeting all the people whose papers I was reading.
Towards the end of my fellowship at Imperial College, Quentin's lab moved to the Sir William Dunn School of Pathology in Oxford.
We had just published our virological synapse paper in JEM, and I knew the best thing for me to do was to stay with Quentin and move to Oxford University and capitalise on that. It was competitive field and I knew I should stay and maintain the momentum and publish more to build my reputation and CV, and give me the best chance of getting funding to get to my goal of having my own lab.
Oxford was another formative experience and the Dunn School was really a leading department in immunology. Towards the end of my time in Oxford, when I was discussing writing a fellowship to start my own lab, Quentin was incredibly generous in letting me write a fellowship on HIV cell-cell spread and T cells. This support was essential and I know many PIs do not support postdocs taking the work with them when they leave, and I will always be indebted to Quentin for that.
Later, I was awarded a MRC Career Development Fellowship to start my own independent lab at UCL.
There were challenges of moving to the UK for my postdoc – namely the change in the pace of science, the work we were doing was exciting and there was more of a feeling of trying to get things done first and to keep an eye on what the competitors were doing. It was a different experience working on HIV in London from rotavirus in Melbourne. HIV had so much more funding and people working in the field and it was exciting to be part of it.
I already new I wanted to start my own lab, so was working hard to make sure I got papers out, built my reputation in the field and wrote a fellowship that would get funded to start my own lab. At first, I didn’t get the MRC Fellowship but I tried again and got it the second time - you can’t give up in science at the first set back.
When I started my own lab at UCL it was just me until I hired a postdoc. When you are starting out as a PI you have to do everything - all the experiments, analysing the data and thinking of what next, writing the papers, writing the grants, managing the admin, training and supervising all the staff and students - it was hard work. But I still remember the excitement when my lab published its first paper.
Could you briefly explain your work today?
My HIV work still has a link to understanding mechanisms of how HIV spreads between T cells but we have branched out. My lab works on the cell biology of virus infection - our HIV work is currently focussed on what makes a T cell permissive to HIV infection and how the virus reprograms cells to make them better hosts for viral replication.
Most recently we have discovered that HIV can infect resting T cells, that are generally thought to be non-permissive to HIV infection, because the process of cell-cell spread reprograms resting T cells to overcome blocks to infection. We have used this to discover HIV uses its VpR protein to make resting T cells gain characteristics of tissue-resident T cells, which has implications for HIV reservoir formation and thus cure. Our current HIV work is therefore very much focussed on permissivity and reprogramming of T cells by HIV, and the consequences for the virus and the host.
However, like many virologists we also pivoted to SARS-CoV-2 in 2020, and we started working on SARS-CoV-2 and innate immunity. In this area we are very much focussed on understanding how CoV-2, as a novel human virus, was able to evade innate immunity which is a potent first line defence against pathogens, and how the variants of concern have evolved to better evade and antagonise innate immunity and the implications of this for CoV-2 adaptation to host and transmission. I guess we have gone from an HIV lab to a pandemic viruses lab!
What inspires you about your work?
I love doing discovery science. I love finding out how cells and viruses work. I love working with the team in my group and our collaborators to make new discoveries and understand biology. There is always something new to find out.
Working on viruses that are important to human health also brings a different set of rewards, away from the discovery and brings a sense that you are contributing, which was very much at the fore working on CoV-2 during the pandemic.
What makes you passionate about research, science and education?
I think as we saw during the pandemic, science has the power to change lives, and it really brought out the best in scientists. So many researchers dropped everything else to work on understanding the biology of the virus, transmission, surveillance, immune responses, to develop drugs and a vaccine.
Our clinically-trained colleagues all went back to the front lines in the hospitals. My lab teamed up with our colleagues at UCL and others across the UK, Sth Africa and the USA, and it was, and still is, an incredibly collaborative and positive experience, everyone sharing ideas, data and reagents. It made me proud that we were able to contribute.
Beyond the practicalities of doing discovery science, I love the opportunity we get to train and mentor the next generation of scientists. Now I am a PI, one of the things I find most rewarding is supporting the people in may lab, and other junior scientists, to develop their own careers, to forge their research identity and to achieve their goals. I benefitted at all stages of my career from great mentors, and so having the opportunity now to mentor and support others is something I am grateful for.
How did your interest in research and biomedicine start?
I was always interested in science, but originally I wanted to be a physiotherapist – I guess being Australian and my interest in sports made that an obvious choice – but in the end I chose to do science at University. I think what I loved about science was all the options and possibilities, I could go anywhere with science and in any direction of research I wanted. Then when I started my BSc I was drawn the biomedical subjects and that was it.
When you think of the word ‘Curiosity’ how does it relate to you and your work?
I love the freedom of science, that I can go in any direction scientifically I want and that the people in my lab can also “follow the science”. I encourage my group to be curious about their results, and it is more often than not that the paper you write is not the one you set out to do. As a virologist, being curious is important, the viruses have largely figured it out, so if we follow the virus we will almost certainly discover more about cell biology and how cells work.
Outside of work, what are your personal pursuits that help you find some work life balance?
I am Australian so of course it is a lot about sport, watching and playing. I used to play a lot of netball, cricket, touch rugby and go running. I still run but I now go to the gym a lot more– I find exercise is the most important thing for me in maintaining a work life balance and I always make time for that in my day.
I played cricket for the Oxford University women’s cricket team and the Dunn School cricket team . I went running a lot with the Dunn School running group and I played netball in London.
Now, I have a garden I spend a lot of time gardening and growing plants and vegetables. Beyond that, I like to travel, visiting new places and countries is definitely a big part of how I like to spend my holidays.
With the hindsight of having built a successful career what advice would you give to your younger self?
- Find good mentors.
- Pick labs and environments that are successful but also supportive and friendly. I have been fortunate to work with great people, and if you don’t like the place you work and the people you work with, success will be that much harder.
- Be generous with your time and support those around you and vice versa, you are never too experienced to have someone else read your grants and papers and to offer advice and suggestions.
- Be positive, science can be hard but it is important to maintain a glass half full perspective, you need to keep going as things won’t always go to plan, but it is important to have a plan.
- Think about your career ahead of time and where you want to get to, and regularly assess where you are and if you are on track or if you need to adjust, and seek advice.
- Don’t assume things will fall into place, and don’t just let your career happen, make it happen.
- Science can be competitive but the competition can be good to spur you on, but it is important to be nice and collaborative, the relationships you build in science will help you throughout your career.
This article was first published by University of Melbourne's School of Biomedical Sciences.