Inside the lab with James: "I’d rather watch a 90-minute experiment than a game of football"
What is your research about?
The CFTR protein acts as a gate allowing the movement or transport of two chemicals - chloride and bicarbonate - out of cells. Researchers have conducted many studies to understand how chloride transport by CFTR is affected in cystic fibrosis, but they know less about how defective bicarbonate transport by CFTR could lead to the symptoms of CF.
Our Strategic Research Centre (SRC), led by Professor Paola Vergani at University College London, aims to understand more about how common and rare CF-causing CFTR defects affect bicarbonate transport and how modulators like Kaftrio rescue bicarbonate transport.
There are five groups of researchers within this SRC programme. We use different techniques, from studying single molecules to studying cells donated by people with CF. My research focuses on how individual CFTR proteins work.
Why is understanding bicarbonate transport important?
Bicarbonate transport is important for mucus formation, organ function, and immune responses. A better understanding of how the CFTR protein transports bicarbonate could lead to the development of therapies that benefit more people with CF. For example, the transport of bicarbonate by CFTR is different for some genetic defects that cause CF.
What’s a typical day like?
I do experiments four to five days a week. Setting up takes 1–2 hours, then I do my experiments. I’m monitoring tiny electrical currents through one CFTR protein at a time – known as single-channel recording. A good experiment is when I can record the activity for up to an hour or more. CFTR proteins with CF-causing defects often yield shorter recordings.
I block out time to do the data analysis separately, since it takes time to evaluate and analyse the results. It can be quite repetitive, but I don’t mind that. Single-channel data tells you so much about how CFTR works, more than making up for the time invested.
How do you measure electrical activity in something so tiny?
I first learnt how to measure the electrical activity of gated proteins (like CFTR) in my final year undergraduate project with Professor Neil Marrion. I spent about a month in his lab for my undergraduate dissertation, and he taught me the technique.
I enjoyed my undergraduate project using the technique so much, that I then did a Master's by Research with Neil. My current supervisor, Prof David Sheppard, was a co- supervisor on my Masters, and in turn that led me to my PhD studies in his lab.
It was quite intimidating at first and definitely a steep learning curve. The equipment I use has been used for decades now. It's basically the same with one or two adjustments over the years. A big challenge is reducing the electrical noise of your experimental set up so that you can record the signal – these tiny currents – as clearly as possible. This helps a lot when interpreting and presenting data.
What do you love most about your work?
I love doing the experiments. Watching the electrical recordings live is beautiful – you’re capturing the behaviour of one CFTR protein at a time. The patterns look like hieroglyphics – beautiful but they need decoding. Sometimes unexpected results make you rethink what we know.
I do love football but, given a choice between watching a football match or a 90-minute single-channel recording, I’d probably pick the recording – it’s gripping!
How do you relax at the end of the day?
I’ve played football my whole life. I currently play in an amateur league in Bristol, my team’s called Evergreen AFC. I also like going to Plymouth Argyle matches with my brother and Dad, when I’m visiting home and get the chance. I actually learned recently that my Dad and my supervisor, David, who is also from Plymouth, were both in attendance for Plymouth Argyle vs. Santos in March of 1973 to see the great Pele at Home Park Stadium!
Besides football, soon after I started my PhD my partner Caitlin and I got a spaniel puppy called Clio. She helps us to relax, though she does require lots of attention!
What does Cystic Fibrosis Trust mean to you?
I’m very grateful that my PhD is funded by Cystic Fibrosis Trust and hope that this will lead to a career in CF research. There’s a strong CF research community, which it is great to be part of. I’ve had the opportunity to meet other researchers at Trust events and research conferences. They’ve been an invaluable help.
Despite improvements in treatments, cystic fibrosis is still a cruel condition without a cure and there is so much more to do to stop CF damaging and shortening lives.
Our generous partners and donors are helping us to fund these research awards and harness world-class research to help improve the quality of life for people with CF. We need your help to fund more research, speed up progress, and make sure everyone with CF can live a life unlimited.
Our research goals
Through our research goals we will accelerate progress towards a future where everyone with CF can live a life unlimited.