Lucy Collinson is Head of the Electron Microscopy (EM) Science Technology Platform (STP) at The Francis Crick Institute (the Crick), London, UK. Lucy completed her PhD in microbiology before switching to cell biology and microscopy for her postdoc with Colin Hopkins. Her first core facility position was as Head of EM at the Laboratory for Molecular Cell Biology (LMCB) at University College London before moving to the Cancer Research UK London Research Institute (LRI) and then the Crick. We caught up with Lucy to discuss her career, the volume EM revolution, FocalPlane and the upcoming JCS Special Issue on ‘Imaging Cell Dynamics’, which she'll be guest editing with Guillaume Jacquemet.
What inspired you to become a scientist?
I don't think there was any point, either in primary or secondary school, when I thought ‘oh, I want to be a scientist’. It was just a case of I enjoyed biology, so I did a degree in biology. Then, the natural progression was a PhD, and so I applied for PhD positions.
Can you tell us about your career path so far?
I did my PhD in medical microbiology with Mike Curtis at a Medical Research Council unit at the Royal London Hospital, Queen Mary University of London. Mike was working on Porphyromonas gingivalis, a bacterium that causes gum disease. I spent my time growing these anaerobic bacteria and doing lots of biochemistry. Then, I switched to cell biology for a postdoc with Colin Hopkins at the LMCB. At that point, I hadn't done any of my own microscopy, but Colin had his own electron microscopes and his own confocal, so I learned how to use the microscopes in his lab. I had really good people training me and supporting me, including Clare Futter, who was my day-to-day supervisor and a key expert in the field.
Did you choose to do a postdoc in Colin's lab because you wanted to learn microscopy?
Actually, I don't think I had realised that it might involve a lot of microscopy. When deciding where to do my postdoc, I was looking for research that grabbed my attention. I went to four or five different interviews and, having talked to both the lab and Colin, studying the formation of lysosome-related organelles was the one that really grabbed me.
While I was doing my postdoc, the lab moved over to Imperial College London. There weren't many EM facilities at that time, so a lot of people wanted to collaborate with Colin's team. This meant that, as well doing my own work, I collaborated with Miguel Seabra, Dan Davis and others, and I really enjoyed it. Then at the UK membrane trafficking meeting, I found out that the person running the LMCB EM facility was leaving. I thought the position sounded interesting, and I decided to apply. I was interviewed by Dan Cutler and Alan Hall, and I got the job and moved back to the LMCB.
From the LMCB with an EM team of just you, you moved to the LRI where you had a much bigger team; what advice would you give to scientists managing a large team?
When I moved to the LRI, that was the first time that I'd ever had any line management duties. There were three or four people in the team when I started as the head of the facility. The Director of Operations at the LRI got me some training in how to manage people, and it's a good job that she did because it's one of the hardest things. It has been a process over the years, learning how to manage a team, including how to do that alongside my other commitments.
When I started at the LRI, I talked to all the group leaders; to learn about their research, see if they had a need for EM and discuss what it could do for their science. Over time, more and more groups started using EM, and as the number of projects built up, we were able to build our team. You normally build the team retrospectively; when we had to put a waiting list in place because we were over capacity, we had good justification to go to management to discuss hiring a new person. When we moved over to the Crick, which is about three times bigger than the LRI, the team grew. We now have around ten electron microscopists in the EM STP; a Chan Zuckerberg Initiative (CZI) Imaging Scientist, Helen Spiers; as well as a small microscopy prototyping group of two physicists and a computational undergraduate sandwich student, run by Martin Jones.
Do you have any advice on setting up effective collaborations?
Everything we do in our day-to-day work, working with scientists at the Crick, is a collaboration. At the beginning, it is important to have a proper meeting with the group leader and the PhD student or the postdoc so we can understand their research question, review any preliminary data and discuss what would need to be in place to do the EM. I think that it should be a very close collaboration all the way through, so communication is really important. EM can take a long time, which means I try to moderate expectations about how quickly the results are going to come back. It can be quite tricky because I tend to sound quite downbeat about the chances of it working. I don't want anybody to be disappointed, but normally when you get the first successful set of images back, they're usually blown away, especially if they haven't done EM before. At this point people get on board, and they don't mind waiting longer and work with you more closely. The project then normally gets more ambitious and extends past the original aims!
For the big technology development projects, it's important to be engaged with the whole community, especially networking with other people who run core facilities. Our collaborations also extend outside of the EM community. We work with people in light, X-ray and ion microscopy, and we also keep an eye on other technologies. In the past, there wasn't a strong link with genomics and proteomics, but as these are moving towards spatial information, there's a big question around how to combine these technologies with ultrastructure.
We also begin collaborations by networking at technology-specific conferences. For these types of collaborations to take off, you need the right calls at the right time from funding bodies. For a long time, we were trying to put proposals into calls that didn't necessarily fit because the funders weren't putting funding directly into imaging. Right now, there's a huge amount of focus on imaging, with the CZI having an imaging programme, and other funding bodies also supporting the development of imaging technology.
Do you also collaborate with microscopy companies to look for solutions?
Yes, it's important to have a close relationship with the microscopy companies. We're buying commercial solutions from them, so you need to know what they're working on, what might be coming next and what the upgrades are. Building these relationships is important because it means you can get early access to systems to test them and even have some input into the development. It's a career-long relationship; some of the people that I'm collaborating with in the companies are the people that I met almost 20 years ago.
You have spoken about volume EM being a quiet revolution – although perhaps it's not so quiet anymore – can you tell us about the technology?
Yes, I think there might have been a couple of people calling it a quiet revolution, and it's difficult to work out who said it first! It has been up against some very exciting, prominent technologies like cryo-EM and super-resolution light microscopy. It took a while for the volume EM community to get our voices heard. It's important to get the message out because it helps research scientists understand what the technology is, how it is used and what it can reveal for their research questions. Getting the message out also attracts funding, which means that people can afford to buy the technology and to develop it to support next-generation research.
We have recently come up with a community definition for volume EM, but I think that will probably change as the field progresses. Currently, we say it's any method that generates serial images of ultrastructure, through a continuous depth of more than a micron, from resin-embedded cells and tissues. I think that will change because there are cryo-techniques that do something similar, like cryo-focused ion beam scanning electron microscopy. These techniques are more recent, and at the beginning it wasn't clear how well they would be able to image cells, but it's looking extremely exciting now. Then, there are related techniques like X-ray microscopy, which I think could take over from volume EM for some samples and some questions. The volume EM community is non-exclusive and open to new technologies. Of course, most of volume EM is correlative because you can still only image a very small field of view with an electron microscope, so you need correlative workflows to pinpoint and track the regions of interest. So far, most correlative work is driven by the EM community because of the complexities of sample preparation and the specialist environmental conditions required to host high-end electron microscopes. But I think with development of more user-friendly sample preparation techniques and technologies, correlative imaging will also be driven from the light microscopy side. Critically, adopting sample preparation protocols that preserve ultrastructure will also likely improve the accuracy of techniques like super-resolution light microscopy and high-resolution X-ray imaging.
It's important to get the message [of volume EM] out because it helps research scientists understand what the technology is, how it is used and what it can reveal for their research questions.
What do you get most excited about: answering biological questions or making technological advances?
For me, they absolutely go hand in hand; you need the latest technology to answer more and more complex biological questions, but without a biological question to constrain you, you won't develop useful technology. You could have an idea for a new piece of sample preparation hardware or a new microscope type, and if you develop it with only a benchmark sample, there'll be a lot more work to make it useable for other applications. I think that making a technology widely used is everybody's aim.
Then, there's nothing like sitting down and speaking to a leading scientist about cutting-edge cancer research or infectious disease research and discussing how imaging might contribute to understanding disease progression and treatment. That's cool stuff to talk about: how you got there, the technology you used and what it means in the context of human health.
Has mentorship been important for your career, and what is your approach to mentorship?
I think that mentoring is a fairly new concept in the timescale of my career. When I was doing my PhD and postdoc, you had your supervisor or the head of your team who mentored you for your technical research, but not so much in terms the softer skills. It was more about peers for me, especially when it came to running core facilities, because they were very new when I was starting out. The rise of core facilities and the push to centralise these technologies happened very quickly, and it meant that the first generation of core facility heads had to work out how to do it on the job. The Royal Microscopical Society played a key role in my field in supporting facility manager meetings where we'd compare experiences and work out how to put processes in place to effectively run our facilities.
I've only started formal mentoring for other people in the last few years. Initially, I didn't think that I had much to contribute, but then I realised that the questions that my mentees were asking were the kind of things I took for granted. I've been working with undergraduates, PhD students and facility leads, and I have had to delve quite deep into my memory for questions around applying for PhD positions! We've also been discussing soft skills like managing people, getting grants, writing papers and giving talks, but I think that often you just need to be there to listen. I enjoy it, and I think I learn as much from my mentees as they do from me.
We've also been discussing soft skills like managing people, getting grants, writing papers and giving talks, but I think that often you just need to be there to listen.
You've been involved in citizen science and outreach projects, could you tell us about them and why you think they are important?
The citizen science stuff is so cool. Applying it to our EM image analysis challenges was Martin Jones' idea. When we started, Cancer Research UK was already working with the Zooniverse (https://www.zooniverse.org/), who are our partners for citizen science. It took us a while to work out how we would set up a citizen science project with data as complex as EM images and to decide exactly what we were going to ask the citizen scientists to do. We started thinking about this around the time that deep learning was starting to make an impact in imaging, and when we realised that we were going to need ground truth segmentations to make the models, we thought that this would make a good citizen science project. When we started, most of the citizen science projects on Zooniverse were related to astronomy or ecology, and we had one of the first citizen science projects looking at biological research. Helen Spiers, who was the biomedical lead for the Zooniverse at the time and is now also a CZI Imaging Scientist at the Crick, worked very closely with Martin and me to set up the projects. We've now moved on from our first project, Etch a Cell, where we asked people to draw around different organelles, to what we now call the Etchiverse – the universe of Etch a Cell projects. We have projects asking people to segment lots of different organelles, such as the nuclear envelope, mitochondria and endoplasmic reticulum. There are only a certain number of organelles that you can recognise by morphology alone, so with the most recent project, ‘Demolition Squad’, we're looking at segmenting lysosomes, but to do this you need correlative data, a fluorescence signal on top of the EM image, to say this thing is a lysosome. Our projects have been really popular, and the citizen scientists went through the data much faster than we thought they would. Some citizen scientists are more accurate with their drawing than others, and so a key part of the project has been to take segmentations of the same image from multiple people and work out how to merge them to find the right line. Incredibly, the original work for this was done by an undergraduate sandwich student, Harry Songhurst, who spent a year in the team as part of his degree course. Martin and Helen then collaborate with our Software Engineering and AI team at the Crick, led by Amy Strange, to use the aggregated citizen science data to train deep learning algorithms. The team are now trying to get the algorithms into more accessible formats because often the end users, the microscopists or bioscientists, don't code and don't use the command line, and it's not necessarily easy to deploy them. That's the next phase. In terms of engagement, the key part is that the general public are contributing to real science, which is recognised by co-authorship on papers. In the author list for the nuclear envelope paper, they are referred to as ‘The Zooniverse Volunteer Community’, with a link that points to a list of the 5000-plus usernames of the volunteers.
For the outreach work, the team and I are science ambassadors at two primary schools in Camden. The Crick has an education team, which is amazing, and we get support from them to go out to work with the schools. We have worked with an amazing teacher who has given us a lot of training in how we should be designing our classes to fit with the curriculum. We've done two years of classes; the last one was around Halloween, and we did some stuff about X-ray microscopy, so we got to incorporate skeletons! We also go into secondary schools, where we give talks about careers in science, and we have work experience students coming into the lab. Now, going to degree level, we currently have an intern from the ‘10,000 Black Interns’ programme. They've been with us for eight weeks, working on real projects and learning what it's like to be in the lab.
It sounds like you and your team are very busy, approximately how many projects are you working on with Crick scientists each year?
It's usually between 80 and 100 a year. The team does most of the hands-on work, but we do train super users. We have around 40 to 50 super users, and they tend to be doing microCT or scanning electron microscopy because you don't need to use an ultramicrotome or use toxic chemicals in the sample prep workflows. We also have some researchers that are fully trained electron microscopists in Crick labs, who are almost adopted members of the EM STP, which extends our capacity to support science at the Crick. I think that sample preparation is where we need to work to make EM more accessible, to make it as easy to do as light microscopy.
As a member of the FocalPlane Scientific Advisory Board, how do you think FocalPlane can benefit the microscopy community?
I think that FocalPlane is an important communication tool, and it is quite unique in the newsletter format that comes into your email inbox. FocalPlane showcases researchers and imaging scientists from different geographical locations, and I've really enjoyed the current collection of interviews with scientists from Latin America. These interviews make you aware of where techniques are being used; you're introduced to people who are working with the same technology as you, and you might see places where you can network and collaborate on fundamental and cutting-edge imaging technology. I also enjoy the technical posts that cover the basics. I've read a lot of the posts on bioimage analysis. I've had a few forays into coding, but I've accepted that at this stage of my career I'm not going to retrain to the point that I can do anything useful; however, understanding the basics makes it easier for me to communicate with our experts in image analysis.
What sort of papers are you hoping to handle in the upcoming JCS Special Issue on Imaging Cell Dynamics?
For the JCS Special Issue on Imaging Cell Dynamics, I am hoping to see diverse papers that cover a range of imaging modalities (light, X-ray, electrons and ions), different stages in the imaging workflow (probes, sample preparation, imaging and analysis), and some interesting new combinations of imaging and spatial analysis technologies operating across different scales. I also hope that for every demonstration of a new imaging technology or workflow there is some thought as to how it will be applied to real life science research, in terms of different applications and in terms of usability and reproducibility in local labs and facilities.
Could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?
I love cheese! For one birthday, my brother got me a cheese tasting experience at Neal's Yard Dairy, a cheese shop in Covent Garden. I got on so well with the lady who runs it, she asked me if I'd like to go and work there as a Christmas cheese temp. So, I took leave from work and worked there for ten days before Christmas. It was amazing; part of the job was tasting each piece of cheese as you gave the customer a taste, because the batches of cheese are all slightly different. The only problem was that after ten days I had indigestion and I was dehydrated from all the salt. So, it put me off for about two weeks, but I'm definitely back on cheese now!
Lucy Collinson's contact details: Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK.
Lucy Collinson was interviewed by Helen Zenner, Online Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.