Our 2020 Society for Endocrinology Dale Medal winner, Frances Ashcroft, is Professor of Physiology at the University of Oxford and a Fellow of Trinity College Oxford. She will be talking about her fascinating research on ion channels and their role in insulin secretion during SfE BES 2020 Online. Find out more about her career and research and get some invaluable words of advice in this interview article.
Tell us a little about your current research
My research interests are ion channels and the metabolic regulation of insulin secretion. These two fields come together in our studies of the role of ATP-sensitive potassium channels in insulin release. I am excited to understand how the metabolism of beta cells works, and how high blood glucose levels in diabetic patients change these beta cells, so that they don’t secrete insulin anymore.
Can you tell us about your career path and what you are most proud of?
I did my undergraduate and graduate studies at the University of Cambridge in zoology. I then did post-docs in Leicester with Peter Stanfield and Los Angeles with Susumu Hagiwara, where I worked on calcium and potassium currents in muscle. After this I set up my own lab in Oxford and chose to study beta cells. I used a technology called patch clamping to look for ion channels closed by glucose. I was a total novice at patch clamping and I was fortunate that others helped me get started and that I got a grant to do it. I have always been led by the science and followed what I am interested in, which in my case is ion channels. I have written a popular book on this subject called the Spark of Life.
I’m most proud of the success of all the brilliant students and post-docs who have worked in my lab. It’s also been wonderful to meet some of the neonatal diabetes patients who have been helped by our work. Andrew Hattersley and his team found that 50% of neonatal diabetes cases are due to mutations on the ion channel I had been working on for 20 years, and we were able to show that these mutations impaired the ability of ATP to close the channels and thus prevented insulin secretion. However they could still be closed by sulphonylurea drugs. This was very exciting because it enabled the patients to transfer from insulin injections to oral tablets.
What inspired you to choose endocrinology as a career?
When I was an undergraduate it was thought that electrical activity was mainly confined to muscle and nerve cells, so I remember being fascinated at finding that it also occurred in endocrine cells, like pancreatic beta-cells. When I took up an independent position at the University of Oxford, I decided to work in a field that was different from my previous one and where there were people at Oxford with whom I could collaborate. I picked beta-cells because of their interesting electrical activity and because I met Stephen Ashcroft, who was working on the biochemistry of insulin secretion. It was the start of a long and happy collaboration.
What do you enjoy most about your work?
There are three main things I enjoy most about my work. Firstly, making discoveries – there is nothing quite like the exhilaration of finding out something new. Secondly, seeing the people who have worked in my lab flourish is a constant joy. And finally, the wonderful long-term collaborations I have had with some outstanding scientists, such as Steve Ashcroft, Patrik Rorsman, and Andrew Hattersley.
How has the COVID-19 pandemic affected your research?
Lockdown was a twofold problem because it prevented us from working in the labs. It was also impossible to keep all of our animal colonies going because of reduced staff in the animal house. We are back in the labs now, but social distancing means that we cannot work at the same intensity as normal. There’s also a constant low level of anxiety about the virus that affects everyone.
What will you be presenting during your lecture at SfE BES online 2020?
I’ll be talking about our work on the role of the ATP-sensitive potassium (KATP) channel in glucose-stimulated insulin secretion. Glucose has to be metabolised by the beta-cells for it to stimulate insulin release. This is because metabolically generated ATP closes the KATP channel, thereby triggering electrical activity, calcium influx and insulin exocytosis. I’m going to show how mutations in the KATP channel that impair ATP inhibition cause neonatal diabetes and increase the risk of type 2 diabetes. I’ll also talk about how chronic hyperglycaemia impairs the metabolic generation of ATP, reducing insulin secretion and speeding the progression of impaired glucose tolerance to full-blown diabetes, and what this means for diabetes therapy.
What do you think about the move to virtual meetings?
The biggest benefit is that you don’t have to travel – which is both good for the planet and saves a great deal of time. Another benefit is that if the talks are posted online, you can listen to bits you’re particularly interested in again at your own convenience. This means you don’t run the risk of missing a talk because another you want to hear is scheduled at the same time. The drawback is that you don’t get to meet your colleagues in person and you miss out on those unexpected and stimulating conversations that lead to new collaborations.
What do you think will be the next major breakthrough in your field?
I think this year has taught us that making any predictions about the future is very unwise, because we never know what’s going to come around the corner!
Any words of advice for aspiring endocrinologists?
My best advice is to ‘find a friend’ – a good person to collaborate with who you not only admire scientifically, but whose company you enjoy. My collaborators have supported me through the inevitable difficulties a scientific life throws at us, have celebrated with me when things went well, and are endlessly and wonderfully stimulating to interact with.
I also think it is important to do what makes you excited and follow what you are interested in. As science is a hard field, unless you love what you are doing, it is perhaps not the best career for you. I’d also recommend you remember Churchill’s advice – never, ever, give in. Perseverance gets you a long way in science.
You can hear Prof Frances Ashcroft’s medal lecture “Metabolic regulation of insulin secretion in health and disease” during SfE BES 2020 Online on Wednesday, 18 November, at 13:05-13:35 GMT. If you haven’t already, register for SfE BES Online now!