Jeremy Carlton studied Natural Sciences at Cambridge University and then joined the lab of Pete Cullen for his PhD at the University of Bristol to work on membrane trafficking pathways regulated by the phosphoinositide-binding family of sorting nexins. He then moved to Juan Martin-Serrano's lab for a postdoc at the Department of Infectious Diseases at King's College London as a Beit Memorial Research Fellow. There, while setting out to study how the ESCRT machinery is hijacked by HIV-1 during viral budding, he discovered a key role for ESCRT proteins in the final stage of cell division. Jeremy set up his independent research group in 2012 at the Division of Cancer Studies, King's College London, as a Wellcome Trust Research Career Development Fellow. He is now a Wellcome Trust Senior Research Fellow and his lab, currently seconded to the Francis Crick Institute, investigates membrane and organelle remodelling during cell division. We have previously interviewed Jeremy (doi:10.1242/jcs.242982) in this series and now caught up with him again after he was awarded the Hooke Medal by the British Society for Cell Biology (BSCB).
Congratulations on winning the Hooke medal! How do you feel about receiving this prize?
I'm very surprised and super grateful! When I got the email that they had chosen me for the medal, I was completely shocked and couldn't believe that my name will be on the list after all those other worthy recipients. The BSCB is an incredibly relevant society for me and is run by amazing scientists that I like and respect, so receiving an accolade from them is a real privilege.
You told me that when you got the email about winning the award, you were in the middle of running a Science Museum Lates event on CRISPR. Is public engagement something you enjoy, and why do you think it's important?
I do really enjoy public outreach, whether it's for school kids, adults, or anyone else. It's incredibly fun to present to a crowd that is almost entirely non-critical (very rarely is there a ‘reviewer three’ in the audience) and speak to them about something they haven't thought about before, or get their minds working in a different way. When talking to school kids, you can easily build on what they've learnt already, show them some new findings or technologies, and normalize being a scientist. I think people always need role models to validate their choices, so if we can go out there and be relatively ‘normal’ in a researcher role, and tell students that it's possible for them to become scientists, that can have an important impact – and I'm always very happy to help support, engage and encourage people into this career.
And from your Hooke-medal talk at the BSDB/BSCB meeting it is obvious that you continue to encourage PhD students and postdocs to follow their curiosity and passion
When I was preparing my talk, I tried to reflect on what I've really enjoyed about my career as a scientist so far. I don't think there's any other walk of life where you have such freedom to follow your curiosity and make new discoveries; in my lecture, I talked about how thrilling was the feeling of discovering that cells failed cytokinesis when ESCRTs are depleted. I also strongly believe that if you follow your curiosity, everything in science becomes fun and rewarding.
“I also strongly believe that if you follow your curiosity, everything in science becomes fun and rewarding.”
In a previous interview with us, you mentioned that before discovering that ESCRTs play a role in cell division, you were absolutely desperate to become an HIV biologist. It seems that the COVID pandemic gave you a reason to work on a virus again
That's right! When I started at the Crick, seeing the HIV biologists on the floor above did make me think that I'd quite like to do some virology again (smiles). I really love cell biology, and think that the way pathogens exploit cell biological processes is amazing – studying pathogens is a great way to understand how cells work. When it became apparent that something was brewing at the very beginning of 2020, many questions started ticking over in my head about the cell biology of SARS-CoV-2. I was excited to see how a part of the scientific community under lockdown pivoted their research and started contributing to the COVID research effort; it was also a great opportunity for us to get involved and try to apply a little bit of our expertise to researching the virus. We started working on some of the less-studied SARS-CoV-2 membrane proteins to understand how they localise and what their function is, and began looking at the envelope protein of SARS-CoV-2. It's been a really enjoyable project and a great learning experience about the scientific process – we knew nothing at the start and nearly all of our hypotheses so far have turned out to be wrong! But we're following the data and are happy to have made some cool findings about how this protein moves through the cell, oligomerises and might help deacidify lysosomes – we ought to write this up soon!
You've put a SARS-CoV-2-related study and other works from your lab on bioRxiv; do you post all of your studies as preprints?
Yes, I think it's a no-brainer to put your work on bioRxiv and would like to encourage everyone to do so. It's just so powerful for sharing findings and demonstrating progress. I can remember being terrified the first time we put something out; we were in a trio of co-submissions with Patrick Lusk and Adam Frost, and back in 2016, Adam was very good at persuading us that this was a good thing to do. It's been useful for me to be able to put preprints into grant applications and progression applications at universities. I think that people often worry that they won't be seen by committees as valid, but I haven't had that experience. Preprints have also really advanced how quickly we can do science – just the other day I saw someone tweet about their preprint and I asked for some of the plasmids they used, which they've sent to me already.
What are the scientific questions that currently keep you up at night?
The simple truth is that nothing keeps me up at night; I've somehow managed to compartmentalise my thoughts and can very easily switch off and sleep well! But what stops me from going to bed is when we find something new that we've never seen or understood before – then I can stay up planning experiments and figures for hypothetical papers late into the night.
Could you tell us about the citizen science project ‘Etch-A-Cell’ that you are involved in and describe how it helps your volume EM projects?
Although we do science every day, there are many people outside of our immediate sphere who would love to participate in scientific experiments, but don't have a route to do so. There's a wonderful Citizen Science platform called Zooniverse (https://www.zooniverse.org/), where members of the public can engage with academic work from research labs across the world. For us, the revolution in electron microscopy (EM) has allowed us to move away from two-dimensional images to high-resolution, volumetric images. To analyse these complex datasets, you first need to delineate the membranes and organelles from the background in a process called segmentation. This is still largely a manual process and a real bottleneck in any type of volumetric EM. Lucy Collinson (Crick EM-STP Head) and Helen Spiers (Zooniverse Biomedical Research Lead) had previously created a citizen science project that allowed the public to participate in the manual segmentation of the nuclear envelope. We are now working with Helen, Lucy, the Zooniverse platform and Crick's Scientific Computing Team to allow the public to segment other organelles and will use these segmentations to train machine learning algorithms to segment raw data de novo. Therefore, it's entirely due to the public's work that we're able to perform these automatic segmentations and form new hypotheses from our volume EM data.
You've now led a lab for 10 years. How would you compare the experience of being an early-career PI with doing research as a mid-career group leader?
When you're just starting out, I think it's important that you demonstrate you can use your funding sensibly and make discoveries you can build on in future career stages. So, in the first five years of my lab, after a few false starts, we developed a very strong focus on a specific question – the reformation of the nuclear envelope during cell division – and were lucky to get some good papers out of it. I was very aware that if we weren't successful early on, the long-term prospects of maintaining a lab were not looking great for me. Now that I've transitioned from an intermediate fellowship to a senior fellowship, it's been really nice to be able to diversify my research portfolio and get engaged in a broader range of projects. So, as well as understanding organelle dynamics during division, we're now looking at immune and cancer cell migration and membrane and organelle dynamics during neurodegeneration. These are all connected by the membrane biology theme – although we're sometimes a bit agnostic to the actual question as long as we can keep doing exciting things! Another advantage of being more senior is that I can focus more on helping the career development of people in the lab, whether they plan to stay in science or leave for something else – I would have found that hard in the first years as I was too terrified about taking my foot off the gas.
“Another advantage of being more senior is that I can focus more on helping the career development of people in the lab, whether they plan to stay in science or leave for something else […]”
And what are the main advantages and drawbacks of running a lab as a fellow?
I started my independent career as a Career Development Fellow and will hold a Senior Fellowship until 2028 – so I'll have been on the fellow ‘side’ in academia for quite a while. In the UK, these schemes pay your salary and give you a generous budget for research that lets you recruit staff and hit the ground running. This was absolutely transformative for me, the five-year period of support gives you time to work up stories without needing to reapply for more funding. These fellowships are also investments in people, rather than projects, and I think (hope?) they give you some freedom to make mistakes. But fellowships also come with their own challenges – their time-limited nature and absence of institutional underwriting bring a lot of precarity, and transitioning to something more secure is not always easy. In the UK, we have several different fellowship schemes from many different funders, but at the same time there don't seem to be many faculty appointments generated. One of the things some universities, such as King's College London, have done in the past few years is set up tenure track programs for fellows, which can really help ease this uncertainty, especially since many of the senior schemes that enable you to continue running your lab as a fellow no longer exist.
How much do you need to teach as a fellow, and do you enjoy teaching?
I actually really enjoy the teaching and I do quite a bit. I know there are conflicting ideas around this, including the argument that if you pay your salary through a research fellowship then that obviates you from teaching responsibilities. I think that teaching is an important part of the job for university academics, so I've always been of the opinion that if you want to be treated as a full member of academic staff, then you should contribute to teaching and administrative duties too. I also think that as a fellow, you might save the university your direct costs, but you're still benefiting from the indirect costs of the environment, facilities and infrastructure that make up a functional department. Therefore, I've always tried to contribute broadly and maintained teaching throughout my fellowships. Teaching can also be really great – it's fabulous seeing students you've taught over previous years progress through the system and get onto PhD programmes now, and I really hope they go on to do cool science. I've also experienced how teaching can influence your research; our recent paper on CDK1-mediated control of ESCRTs was something new for us, so teaching undergraduate lectures on the cell cycle really made me learn the biology of it properly for the first time!
Throughout the pandemic, what has been your experience with using remote tools for meetings and teaching?
I've been amazed at how well management and administrative meetings have run on these online platforms. They've been a massive time saver for me, as I don't need to hop on a train to travel to King's in the middle of the day and I think we've all discovered that some degree of multitasking is possible in these meetings! I think they work less well for scientific meetings, and I've definitely missed travelling to in-person conferences as I think you get much more out of them in person, including making new connections and meeting old friends. I'm not sure that we've found a way to replicate that online, but I do recognise that this format makes attendance more accessible for delegates and speakers alike. Regarding teaching, we are now transitioning back to in-person delivery, which I enjoy a lot more than talking to a screen of Microsoft Teams pastel discs, and I think the students will also benefit a lot and be more engaged.
Finally, what do you do in your free time?
I love cycling, but as life got busier, I found less and less time to ride. Then, during the lockdowns, it was a bit of a revelation that instead of taking the train, I could commute by bike – which I've tried to keep doing every day.
Jeremy Carlton's contact details: King's College London, The Division of Cancer Studies, New Hunt's House, Guy's Hospital, London, SE1 1UL and The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Jeremy Carlton was interviewed by Máté Pálfy, Features & Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.