We spoke to David and Jacob about the studentship, how having someone with CF working on the team has changed how David thinks about his work, and what their hopes are for the future of CF research.
What was the focus of your studentship?
Jacob: I was focusing on a new triple combination therapy, not Trikafta, and whether it restored the plasma membrane stability of CFTR. I used a technique that allowed us to measure whether we’ve seen a correction of CFTR; whether the protein is trafficking to the cell surface, but also whether that’s continued over time. So we took data points at zero, two, four and six hours to see whether the number of proteins at the start remained the same or changed over time.
Why did you choose to get involved in CF research?
Jacob: I have CF, and when I was at school I got particularly interested in drug development. Being interested in CF research was just a natural progression of interests, and it led me to look at projects taking place over the summer.
David: There’s a history of people closely linked to the condition making very important contributions to it. Paul Quinton, who’s now over 70 years old and has CF, demonstrated the defect in chloride movement in cystic fibrosis. Jeffrey Wine at Stanford has a daughter with CF, and has contributed a lot to our understanding of mucus and sweat glands. Gunnar Hansson in Gothenburg in Sweden has a son with CF and he’s really at the forefront of knowledge about mucus and how it’s produced and why it has different properties in cystic fibrosis.
But even individuals who aren’t directly linked to cystic fibrosis develop a passion for working in the area. It’s been such a privilege to have had this career and to be able to contribute in a small way to the advances that have been made.
Often with the summer studentships, students take part at their own university. Jacob, you study in Durham, and the studentship is in Bristol! How did that come about?
Jacob: I actually first read about the studentships when I was a sixth form student, and thought, “Right, I’m going to do that!” Not realising that it wasn’t really aimed at sixth form students… I did a bit more reading and thought, oh that’s a shame, that would have been really fun, and then forgot about it.
Then when I was in my second year of university I was reading stuff about CF and thought, this is something I’m passionate about and want to do next summer. So I went onto the Cystic Fibrosis Trust’s website, and scrolled down the SRC list and went through them one by one. I sent David an email at about 6pm and had a reply by 8.40am the next day saying yes!
David: I was at the 2018 North American Cystic Fibrosis Conference in Denver. It’s a hectic meeting with not much time for email, but replying to Jacob promptly was important.
Jacob: Later, David said that we should apply for the Trust’s Summer Studentship programme, and I remembered that I had heard of it all those years ago!
What appealed to you about David’s research?
Jacob: I think I’d always been really interested in the CFTR modulators. In theory, it’s such a simple problem. If we could find one molecule that fixes all the mutations that would be incredible. And I don’t necessarily think that we have to do that, and I don’t necessarily even think that would be the best route to go by. But just the concept that if we could get this protein to fold properly and traffic to the cell surface, and then to work, we’d be done.
There’s a magic bullet that you’re looking for, and that must be very exciting!
So what did you hope to get out of the studentship?
Jacob: I hoped to get a good understanding and fill in my knowledge of CF and CFTR, to get a good set of lab time, and to get used to what research and data analysis is actually like.
And has it lived up to your expectations?
Jacob: It’s been harder than I thought it was going to be. But in terms of what is it really like, it’s shown me that first year and second year labs are not the same as real life research. Real life research is better in a lot of ways – I’ve really enjoyed being in the community of researchers, they’ve been so welcoming – however, the data aren’t always perfect, and that’s been hard. But it’s also been good, because that’s the reality of research.
What were the best bits of your studentship?
Jacob: I’ve learnt a lot of techniques that I’ve never done before. And being around academics and seeing what a PhD is like for six weeks and just spending time in that environment has been a really positive experience. It’s made me realise that doing a PhD is three years of really hard work, which is a good thing to realise now. But it has made me also go: “Wow, this is really, really satisfying, and something I’m really interested in,” even more than I already realised.
Any bad bits?
David: Shall I walk out now!?
Jacob: There was a specific day, where either I killed all my cells, or they all died. Well, it happened twice. Once they just didn’t respond, and the other time I came in one day and there were just none of them. There are supposed to be two to three million cells in a petri dish, but when I put them under a microscope I could hardly see any, and we look for a good, even coverage on the bottom of the petri dish, so they couldn’t be used.
Did anything happen on the studentship that you didn’t expect?
Jacob: I once walked out of the lab to a man in the corridor holding a wooden samurai sword.
David: A world-renowned professor!
Jacob: And he was saying: “Where’s yours? Step up, where’s yours? I want to have a duel with you,” right there in the corridor. I just looked at David like, ‘what do I do?’
And was he joking?
Jacob: Well he’d just come out of a lecture theatre, which he said was the only place he could practice. So I think he genuinely does have a passion for fighting with samurai swords.
Has the studentship given either of you a different perspective?
David: As a researcher, you have some ideas, but you never have day to day interactions with someone with CF, so I think that puts a completely different perspective on things.
Jacob: I enjoyed being able to spend time with people who know stuff about cystic fibrosis. One weekend I went home for a hospital appointment and everyone was really interested. And at the same time, when I took Creon they weren’t wondering what was going on. It’s just, Creon, of course.
David: It was very valuable for the PhD students and the rest of the team. I personally found it very motivating.
What are your hopes for the future of cystic fibrosis?
David: You want to see CFTR modulators and therapies that compensate for the lack of CFTR available and you want to see them available for everybody. Still there’s work to be done, but there’s a pathway to be followed, and you want to see that goal reached and contribute to that.
Jacob: For me, in terms of the next 10 years, I’d want to see a reduction in the treatment burden for people with cystic fibrosis. What we’ve been working on really would do this. The lung damage has already been done, but if we can find a good enough set of modulators, we can at least hit pause and allow people to resume a semi-normal life.
Since this interview took place, Orkambi and Symkevi have been made available in England as part of a two year deal, and we are hopeful that Wales and Northern Ireland will follow soon. Researchers like David are working hard to develop the next generation of CFTR modulators - please donate today to support research like this.