Tell us about your career so far
My first proper research project was in a synthetic chemistry lab as a chemistry undergraduate at the University of Oxford. I really enjoyed the work but realised I was more interested in applying my chemical knowledge to biological questions.
So, I found a PhD with some rotations in the first year, meaning I could try out doing research in a more biological context. I did a six-month project with Chris Schofield (who went on to be my PhD supervisor) and spent another six months doing protein NMR (Nuclear Magnetic Resonance) with Christina Redfield. I combined these into the rest of my PhD project, working on a family of enzymes, known as histone demethylases, which are involved in epigenetic regulation. I discovered a new reaction that some of them could do, known as arginine demethylation.
After a couple more years as a postdoc finishing off projects from my PhD, I was awarded a Marie Curie Global Fellowship. This gave me the chance to move to Tokyo for two years, followed by a return year in Oxford. And that led me here to Imperial College London and the Crick!
What have been the highlights so far?
Being in Japan was really fantastic – it was such a great opportunity to do exciting science whilst living somewhere completely new and different.
Part of the reason I wanted to go was my boss there, Hiroaki Suga, has an amazing technology, known as the RaPID system, that I really wanted to learn to use and apply. It allows you to make enormous libraries of cyclic peptides and screen them against proteins you’re interested in, to find things that bind really tightly to them. This gives you a good starting point for developing chemical tools to interfere with enzyme activity.
Tell us about your research at the Crick
I’m really interested in using chemistry to understand biology in ways that are difficult to do just by, say, genetic methods. Chemistry gives you a new window into modulating biological processes.
At the Crick, I’m combining interests in post-translational modifications I developed during my PhD with the technology from Japan.
Currently, I’m working on a family of enzymes, known as the peptidyl arginine deiminases, that are involved in important cellular processes, such as gene regulation and pluripotency. These enzymes are often mis-regulated in inflammatory diseases, such as rheumatoid arthritis. Like lots of enzymes involved in post-translational modifications, no one really knows how they are regulated or how they end up in the right place at the right time. The technology from Japan gives me a nice way of making tools to find that out.
And what motivated you to come to the Crick?
When I first heard about the Crick I thought it sounded like an amazing place to work, especially with its emphasis on collaborative research and training young researchers. Then when I was out in Japan, the Crick advertised this new scheme for physical scientists applying their research to biological questions.
I thought, that sounds a bit like me! It was slightly before I had planned to be applying for independent positions but it sounded like my dream job so I thought I’d give it a shot – and it worked out!
What are your first impressions of being at the Crick?
That this is such an exciting opportunity! I’ve always worked in traditional chemistry departments before and my research is really at the interface of chemistry and biology. So, it’s particularly nice having the link to both Imperial College London and the Crick.
Overall, first impressions, it’s amazing to have such close connections to all the research groups here at the Crick and to be so immersed in everything. It’s such a collaborative environment and I think it will help me to better understand a lot of my biology, which has mostly been self-taught and picked up along the way. Hopefully, my perspective can help other people with their research questions, too.
How far have you got with setting up your lab?
There’s quite a lot to do and that’s exciting, but slightly daunting, too. I arrived to my empty office and empty lab benches and suddenly felt the weight of expectation!
There are lots of practical things, like purchasing equipment, lab reagents and recruiting people, that you just don’t have to think about when you join someone else’s lab. But we’re lucky here at the Crick, because there are so many people and shared resources to help get you started - I’ve already managed to get in the lab.
Overall it’s been fun and I’m definitely getting there.
What do you hope to achieve while you’re here?
Right now I’ve got lots of ideas. In six years’ time when I move my lab to Imperial, I hope lots of those ideas will have come to fruition.
Firstly, I hope to have made and used tools that will have helped to unravel the roles and regulation of protein citrullination by the peptidyl arginine deiminases. If we make steps forward in understanding how and why enzymes like these go wrong, hopefully we can also improve the ways we treat the diseases they cause.
Secondly, I’m hoping that the methods I’m going to develop can be used by other chemical biologists working on a wide range of enzyme families and diseases. I’d like to think that I haven’t just worked in one small niche but that I’ve provided something more generally applicable.
What gets you out of bed in the morning?
Sometimes it can be easy to get caught up in all the ‘side bits’ of a research career. But, ultimately, someone is paying me to do what I find fascinating. Every day I get to wake up knowing I’m working towards discovering something new, something that might contribute to our understanding of human health and disease, and that’s a pretty nice thing to be able to do.
What job would you be doing in an alternative universe?
Hmm, good question... Outside the lab I’ve always loved music, and still play my bassoon in an orchestra whenever I get time, so maybe I’d be a musician!