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Intro/Outro (00:00:03):
Welcome to The Microscopists, a Bitesize Bio podcast, hosted by Peter O'Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O'Toole (00:00:21):
Hi, I'm Peter O'Toole and today I spoke with a close friend, Lucy Collinson from the Francis Crick Institute about The importance of failure.

Lucy Collinson (00:00:30):
Don't worry about the failures as well. You will fail as part of your career and you will fail to stand up on a surfboard

Peter O'Toole (00:00:39):
Speaking at conferences.

Lucy Collinson (00:00:41):
Yeah, I used to feel sick for a week before a talk.

Peter O'Toole (00:00:46):
And the Eurovision Song Contest.

Lucy Collinson (00:00:49):
And we wonder why we never get any votes at Eurovision.

Peter O'Toole (00:00:56):
In this episode of the microscopists. Hi I'm Peter O'Toole and today I'm joined by Lucy Collinson from Francis Crick down in London, Lucy. Hello.

Lucy Collinson (00:01:13):
Morning Peter how are you?

Peter O'Toole (00:01:13):
I'm good thank you. The first time we met was ELMI I think,

Lucy Collinson (00:01:18):
Yip. ELMI in Nijmegen and which was my first ELMI meeting. And I have to say it's one of my favorites. It's a really good

Peter O'Toole (00:01:24):
I can see why, you met me there

Lucy Collinson (00:01:28):
Well, Yeah, let's leave it at that.

Peter O'Toole (00:01:31):
No let's not that, that that meeting for me was also very memorable for good, well, yes, all sorts of reasons, but I think the most obvious one is a, I think it was Sander who introduced us, was it at the time I was talking to Sander about a potential grant application, thought about it and he said, well I know just the person who, who, who can do this better than I could do it, which was yourself. And that's how we introduced I believe.

Lucy Collinson (00:02:01):
Yeah. I kind of, I remember you guys walking across the the hall way in the middle of the university, very purposefully with with your grant ideas and it sounded really exciting and me going, yeah, yeah, let's do it. Let's do it. And then five weeks later we submitted and we got the grant funding, which is pretty much unheard of

Peter O'Toole (00:02:24):
Yeah and significant as well. At least my largest grant I've ever been awarded. I think with contributions, it was close to 2 million pounds, I think.

Lucy Collinson (00:02:36):
Yep, and we bought a new scanning electron microscope with it. We turned it into a microscope within a microscope with Delmic, which is kind of cool and started a lot of research for us on microscopes in microscopes.

Peter O'Toole (00:02:53):
Which yeah within five weeks. And actually I think the backbone of the application was actually developed on the dance floor around the bar of the conference banquet.

Lucy Collinson (00:03:03):
I mean, there wasn't much food was there, but there was plenty of wine and plenty of beer and I've never seen a group of people dance like the ELMI participants. It was, it was excellent.

Peter O'Toole (00:03:15):
Yeah. I think that, I think that the most surprising thing is that we remembered the backbone of the grant application in the morning because it was a long evening in the end. I was expecting it to finish much early when it went on and on

Lucy Collinson (00:03:29):
It might've been a different grant application than the one we came up with that day, but we got it. So

Peter O'Toole (00:03:36):
Yeah, I think it was a simple ideas. And just, do you know what I think maybe it was a five week turnaround, but it was almost obvious and their quite often the most successful and the ones you don't have to think about too hard. I just thought it fell into place a lot of long hours putting it together though.

Lucy Collinson (00:03:53):
Yeah. But that's, that's not a bad thing when it's exciting and when you, when you know what you want to do and it fits with the grant. Cool. And like you say, it just comes together.

Peter O'Toole (00:04:04):
So, so a lot of that was around correlative lighting electromicroscopy, which is where you've really forged your name and obviously for 3DEM and volume electromicroscopy. So that, that grant application was obviously a highlight, I think. Yeah. What about the low? I think this is probably going to be similar. What, what have you found the most challenging times in your career?

Lucy Collinson (00:04:30):
The, the other grant that didn't get funded, the first big grant proposal that we put in and it was, I'd love the acronym still. And I was, umming and ahing in about whether to to say the name of it, because I don't want anyone to nick it, but it's so good. So we called it IVOXEL which is Imaging Volumes with X-rays Electron and Light it's so good. It's so good because it's all in 3d so it's all VOXELs. And that was with Jemima Burden at UCL and Andy Bushby at Queen Mary. He runs the nano vision center there and he's material scientists and Raffa Carzaniga who's Deputy Head of my facility now, but she was at Imperial college. And the idea was to have a virtual network of volume electro microscopes. And that was pretty early on before we even called them volume EMs.

Lucy Collinson (00:05:27):
So serial block-face SEM and [inaudible] SEM, and it would be open access so that people could send their samples in and run them. And it was probably about 12, 12 years ago, something like that. And we didn't get it and it was the first big failure. And I was so frustrated and it honestly, you know, when you see something and you can, you can tell it's good and you know, it's going to be beautiful, then it doesn't get funded. And ironically, now we're just putting together, the pretty much, similar thing where UK infrastructure of Volume EM however many years later, but the technology is much more mature and the a much bigger community. And I don't know, it feels right. So fingers crossed.

Peter O'Toole (00:06:13):
Yeah, Plug, plug it, plug it quickly. And that, that whole community has moved on significantly, as you said at the start Volume EM wasn't really a, a word, it was sentence,

Peter O'Toole (00:06:25):
No

Peter O'Toole (00:06:27):
Sentence phrase, phrase, maybe the better term to use it, but you've obviously forged your name in Volume EM that, throughout that, but I've got to state that, so that didn't exist as a technique when you started electromicroscopy. But when was the first, your first contact with an electron microscope? When was that?

Lucy Collinson (00:06:51):
So that was the last year of my PhD. My PhD was in microbiology. And actually microbes aren't that interesting to look at, but at the time I was isolating doing lots of biochemistry and isolating enzymes and running them on gels. And after three years of bans on gels, my boss recommended that I give my bacteria to the electrical microscopy facility which I did. And then you get a picture back and it was like, suddenly you can see what you're looking at. And I mean, it's not very, very interesting looking at like gum disease bacterium as there's not much inside it. But each of the postdocs I applied for contained electrical microscopy, I'm not sure that it was, you know, I did it on purpose. It obviously caught my attention. So what year was that? 98.

Peter O'Toole (00:07:52):
Firstly, electron microscopy you then went on to use electron microscopy more extensively straight after that.

Lucy Collinson (00:07:58):
Yeah. So I ended up doing a post-doc at UCL at the laboratory of molecular cell biology in Colin Hopkins lab. And I didn't really have the background for it. Oh, there we go. That's my leaving Do so that's around 2004.

Peter O'Toole (00:08:18):
Yeah. So, so, so the picture we just put on I presume just above my head.

Lucy Collinson (00:08:24):
Yes. So it's above your head is Colin and Colin is a cell biologist. Researches into membrane trafficking. And at the time he was quite unusual because he had his own light microscopes and his own electron microscopes in the lab. So I was taught and got to use the, the electron microscopes as fundamental parts of the project, but I also had to learn what a cell looked like, cause I have no idea because I'd been looking at bacteria, so I didn't know what a nucleus or mitochondria or endoplasmic reticulum or any of that good stuff. It was a very, very steep learning curve. But that photo is really interesting because there's a, there's a whole kind of, I guess, progeny of the lab that have gone out and run the EM facilities around the world. So on your left, as I'm looking at you, Matt Russell is now a member of the EM STP and on your right Also Otto Berninghausen runs a cryo-EM facility in Munich and Jemima Burden now runs the facility at LMCB. So a lot of good Electron microscopists came out of that lab

Peter O'Toole (00:09:32):
And you haven't changed much at all.

Lucy Collinson (00:09:34):
No, you can tell the era by the hair color and the amount of time in lockdown by the grey hair.

Peter O'Toole (00:09:44):
I just keep cutting my grey off. Actually don't I get my son to do it much better. I wouldn't dare touch my own hair, even. He's quite good that nearly at an end though. So hopefully

Lucy Collinson (00:09:56):
Yeah, hopefully fingers crossed.

Peter O'Toole (00:09:59):
So that, so that was your PhD that was doing your postdoc days. Yup. And then what was your next career step?

Lucy Collinson (00:10:08):
I then, so there weren't that many electron microscopists around and you tended to find that you got lent out to other labs to do their electoral microscopy for them as part of a collaboration. So instead of after three or four years instead of having my own post-doc projects, I was working on three or four different projects in collaboration with other labs. And I preferred that I didn't really enjoy just working on one project and getting really deep into it. Umo I bumped into Dan Cutler in a Lift back at UCL at the LMCB where I'd started my post-doc in Colins' lab, but then moved to Imperial. Umnd he told me that the person who was running their facility was leaving. And, m said, well, that sounds like an interesting job. And a couple of months later, I took over running that facility and it was just me, just me and two, u,ectron microscopes and 20/26 groups. Um,d only a couple of them were using the EM when I started in, u,didn't know, about 10, 10 or 12 of them were using EM by the end, but I had to train everybody at that point cause I was the only person there so I couldn't do that amount of work. And that was, that was a little fun training people and working with people.

Peter O'Toole (00:11:35):
That's, A, that's a lot of people, that's a lot of that, that's almost a third of the department or more than a third of the department using the electron microscope, which is, which is pretty rare I think even today to get such a large cohorts of percentage using the electron microscopes, any idea of what it is at CRICK at the moment

Lucy Collinson (00:11:55):
Yeah, we have, so at full capacity we'll have around a hundred research groups there. And at the moment, I think it's about 90/95 we're working with around 60 of them. So it's not that people don't have a need for EM, but I think most of them are put off because,uit's not something they're taught to do hands-on because the sample prep is really complicated and ultra microsomy cutting, cutting ultra thin sections is, is very time consuming to them and, and you have to have a particular type of temperament and you can't drink too much coffee.

Peter O'Toole (00:12:37):
Yeah, actually, yes. It's, it's early in, relatively early in the morning for you. The one thing I was warned about very early on by yourself was that in the first thing in the morning, you're not necessarily the early type I've got a picture of your lab here and they're all wearing hard hats and they assure me anywhere that between nine and ten o'clock in the morning in case they bump into you , is that true?

Lucy Collinson (00:13:03):
Yeah. It's only fair, to warn people that I'm not at my best before 10 o'clock in the morning. I remember the, the only exception early on was if I was giving a talk because I used to get really, really nervous about giving talks and I would panic for about a week beforehand, so I would ask to be on first, just so I could get it out of the way. And my first big talk was at the Society of Electron Microscope Technology in London and I was on at nine. So it was a very fine balance between, you know, not being with it because it was too early in the morning for me, pre ten o'clock and getting the talk over and done with, and then they projector broke down on me. So it kept overheating, it would turn itself off every 45 seconds, and I was talking about some work we'd done with the correlative light and volume EM on zebra fish, looking at blood vessels growing. So I had to mime and that's the process which is blood vessels growing and then fusing, you know, maybe it's good if it's early and you don't have too much time to think about it

Peter O'Toole (00:14:09):
So you're a lot more chilled now, If you caught any of your staff with their boots on one of the EM tables, you would go nuts, and affected your warranty as well and by the way, sorry.

Lucy Collinson (00:14:25):
No, absolutely and I knew I shouldn't have been doing that, but that is a look of absolute relief because that was the first microscopes on the site at the CRICK, after eight years of planning and five years of building. And that those microscopes had been on, on the back of lorries across London and into a new site. So I wiped it down afterwards.

Peter O'Toole (00:14:53):
It's exciting time though, to take up the new, the new role at CRICK and move through, have you ever regretted, moving out of being a pure academic and that type of route and taking more of a core facilities and leading the core facility there.

Lucy Collinson (00:15:08):
No, never. I, it wasn't for me, the, the traditional route through science. I, I didn't have my own research question. But when I started using electron microscopes and light microscopes, it was a technology that really interested me and excited me, and it was pushing the technology forward to be able to answer the biology that really motivates me, I guess, one of the difficult things that you'll have experienced as well as when, cause we're pretty much the same age. So when we started in core facilities, it was a non-traditional career. Uand people tended to think of you as a, a failed scientist. And actually looking back, it's changed. We've had some very dynamic people going into core facilities and, and really building them up and, and driving it as a real career, and as technology gets more complicated, so you need people who have a background in biology or materials or physics or whatever to, to make these things run for particular applications. But, and it has changed quickly and I think now a lot of the researchers that we collaborate with see us as, but understand that we're scientists with similar backgrounds to them, we've just gone off in different directions, but it, it's not completely plain sailing.

Peter O'Toole (00:16:32):
Yeah, you're right. I, I, I posts are clearly not academic in the normal term of academic posts. We don't lead research groups, purely research groups, but I think it's fair to say that we have quite a large influence over the research going on at the Institutes, Universities and even our own teams are academically minded in some cases and driven. I think you're probably one of the leading examples of how in a non-academic post you are very academic still. Uand, and I think there's a delicate balancing act from having your own research interests and also which, which is technology advancement more than answering a biological question, because I think it's fair to say similar to myself, you're a technologist interested in advancing the technology for the users. And then also being, keeping that balance that our teams are still so reorientated. I think

Lucy Collinson (00:17:31):
I'm allergic to the word service, as soon as you say service, people think that they can just bring you a sample and give it to you and say, I want a pretty picture for the end of my paper. And actually what we do is, you know, you have to collaborate, they have to put the effort in and tell you the whole story behind their research and, and you know, what they want to see and therefore what resolution you need and which probes you need to get into the samples and how you're going to prepare them. And now there are as many different correlative workflows as there are research projects. So everything is custom designed to the research.

Peter O'Toole (00:18:05):
Yeah, I think I know from some of our side, I do see us as a service at York for some, some instances, but it's pretty routine turn handle get results out, but not in all cases, clearly not in all cases. And they're the ones I, as you, I think the team and myself enjoyed both sides of that. I don't, I don't think service is a dirty word. I think we still serving and we're still part of their team. We're still adding value, we're still going to be inputting into their research, but at a different level, I think it's that, that extra level and taking it beyond what they've come and asked for. And that's certainly what you've been doing in a significant way. I think citizen science is just one example of that, of how you've, you've got a problem from users and you've taken those problems and moved it forward. Uh,u found a solution. So I think this backdrop is from what, Lucy, so I've got a very icy picture here.

Lucy Collinson (00:19:07):
Yeah. That's that's Chicago last year in march. It's really cold in Chicago in March. We just missed the, the deep freeze, but that's looking out from the meeting room at the Adler Planetarium,uover the Lake, which was completely frozen. And,uyeah, yeah, the reason we have a citizen science project is because of microscopes like this, this is our focus. Uit's the five forty, crossbeam five forty,uwhich the focused ion beam scanning electron microscopes. So we have our cells and tissues embedded in resin. We use the ion beam to mill away, very thin slices, five or ten nanometers. And then you take an image and then you mill and image, mill and image, and we can collect thousands of images in a week. Uand milling at that scale, even at, to image through an entire cell, just one entire cell would be, say three to 5,000 slices.

Lucy Collinson (00:20:07):
So then your, your data is up in the terabyte rating and we just can't analyze the data quickly enough. So you can't extract all the meaning from it, a 2d slice. Doesn't tell you very much, but if you can convert that into a 3d model of the cell with all of the organelles, then you can start to be quantitative and compare screen health and disease. So we were a bit stuck and we have the EM side of the team who were working on research projects. And then we have the microscopy prototyping side run by Martin Jones. Who's a physicist and Martin and his team build new hardware and software, so it was actually Martin's idea to go to citizen science, because now we're in the era of machine learning. I'll tell you what he's holding in a second. So now that we're in the area of machine learning, what you really need to train computers to recognize organelles automatically is ground truth, which is, normally means us experts sitting in front of the computer and drawing around saving nuclear envelope in thousands of slices. So it takes a week to get the dataset in fair. Yep.

Peter O'Toole (00:21:27):
Then how long for that expert to analyze that data to, to, to draw around it and make a 3d volume of it.

Lucy Collinson (00:21:35):
So you just for the nuclear envelope which is the membrane surrounding nucleus, and that's also what Martin's holding, that's lit up in red that would take another week and that's just one structure inside the cell that's in, you know, not even thinking about the other organelles, like mitochondria and enplasmic reticulum, golgi, etc, etc,u

Peter O'Toole (00:22:00):
I'm fully impressed it's only a week to actually do that.

Lucy Collinson (00:22:02):
Yeah, well guys in the lab are really good, but that's one cell one week working on nothing else than that, you know, very long.

Peter O'Toole (00:22:15):
So statistically not very robust.

Lucy Collinson (00:22:15):
Statically Insignificant. Um, we, through Martin's original idea, we collaborated first with CRUK and then with the Zooniverse, which was set up by Chris Lintott, in Oxford and he uses citizens or the general public to, u,lp him classify galaxies. And his project went, so this is back in about 2008 and his project went so well that, u,laxy zoo, his original project became the Zooniverse and the Zooniverse now hosts a huge number of different systems science projects, and we have one of the first biomedical projects asking the general public to do this drawing and to reconstruct organelles for us. So this one and the one that Martin's holding is the first nucleus that was completely reconstructed by general public.

Peter O'Toole (00:23:08):
Can you trust the General public to, to draw and annotate it properly?

Lucy Collinson (00:23:12):
Well, I always said, no. I always said you had to have 10 years experience looking at EM images to be able to understand them and interpret them. And I was completely wrong. You've got, you've got that audio recording of me saying, and I was completely wrong now. It turns out that you give, give them a, a few short instructions and people do a pretty good job, we get some graffiti some of which we can show and some of which we can't. But Martinand Helen Spiers who's from the Zooniverse to cognitive, who's their biomedical lead and our digital development team at the CRICK are able to automatically remove the graffiti they've designed algorithms to pick out the right line from all of the different citizen science annotations and then train the first machine, learning outlet them and say the papers almost ready to buy, or archive which is really exciting.

Peter O'Toole (00:24:14):
That's actually related to research then, how many citizens? So just, just Joe public, just, you know, these aren't scientists necessarily, these are hired people in many cases.

Lucy Collinson (00:24:26):
Yeah. We, you, you get to know, so there are chat boards on the site, so you get to know some of your citizen scientists and early on one of the people we went through, the entire data set that we put up,ureally quickly was a, a grandmother in the US who had broken her ankle and she didn't have anything else to do so she, she did all of the images and then asked for some more,uwe have, we have schools doing it. Uwe, I've just been asked by a couple of people for references medical school for their contributions to the project. So, and, and it's building, so we now have a mitochondria project out, we're working on an ER project and, and,uthen we'll hopefully start putting up some really kind of cutting edge CRICK research on there,uand pushing forward into virtual reality as well cause at some point we're gonna have to visualize these things and turn them around and start to understand that 3d shape and structure and what that means in biological terms.

Peter O'Toole (00:25:27):
So how many volunteers have inputted so far?

Lucy Collinson (00:25:31):
It's on the, on the first nuclear envelope project, it was around 5,000 and we had around 150,000 lines drawn. That's actually quite, quite a low number for the Zooniverse. They have about, I think, a million and a half, 2 million volunteers you interact with their platform. But a lot of those projects are saying yes or no to questions, whereas, ours, people actually have to sit down and really interact with the data. So there are, there are fewer people.

Peter O'Toole (00:26:04):
Yeah. I, I think maybe as word gets out and it passes around more. I think the importance of what they're doing is huge. I mean, this is, this is them volunteering and helping solve very difficult questions, which ultimately aids cancer research significantly, I guess that gives them a sense of reward. But just looking at your image, which looks like a load of fabric web. So I guess it is a virtual knitting,

Lucy Collinson (00:26:32):
Well maybe that's the next step public engagement projects. Maybe we'll get somebody to crochet a nucleus. We can have a whole, I think they did that up in Scotland. One of the institutes I visited, I think they had knitted a cell, something which was in the middle of their atrium.

Peter O'Toole (00:26:51):
Wow. So, so this is going to be published soon.

Lucy Collinson (00:26:55):
Yes

Peter O'Toole (00:26:55):
Uh,

Lucy Collinson (00:26:56):
Well, Aye or archived

Peter O'Toole (00:26:59):
I'm not going to ask you a difficult question and I'll allow you two, if you can't think of one, but what is your favorite or most favorite publications that you have been part of? Good question

Lucy Collinson (00:27:14):
It's usually the most recent one because every paper has a huge amount of effort from the guys in the lab. Uso that our most recent one is with Eva Frickel from, mirmingham and Imperial college, looking at toxoplasma parasites in zebrafish brain, msing zebrafish as a new model for studying infection and Marie-Charlotte in the lab has just done some incredible correlative light in the EM in 3d. And, you know, we're lucky we have, we have a whole range of microscopes so we can pick and choose them as we need for the biology. So she's used, this is real needle in the haystack thing. So it's holes over fish brain with these tiny parasites. And, mo she's used x-ray imaging to locate them. There's, meally beautiful fluorescence imaging of the parasites and macrophages. And then we have serial-section TM focused on SCM and serial-block face SCM of around 40, something like 40 different parasites. So it's, it's, I guess the beginning of our volume EM work was back looking at, hlood vessels and angiogenesis with Holger Gerhardt's lab again in zebrafish and that was the core cyst correlation that it was all we could do at that point. And the most recent zebrafish paper is I think, shows how far we've come in the last 10 years or so.

Peter O'Toole (00:28:50):
So like where was that published?

Lucy Collinson (00:28:53):
That's a really good question. It's bio archive, but it's just being accepted. I need to double-check

Peter O'Toole (00:29:03):
There I'm giving you a plug the opportunity to increase that pack factor.

Lucy Collinson (00:29:09):
I know you can tell that it's, you know, I'm really thinking about this as you were asking me, it's not pre pre prepared

Peter O'Toole (00:29:17):
That also shows that it's not about where it's published. It's about the fact that it is published and out there for the public to read that is more important.

Lucy Collinson (00:29:26):
Yeah. Like in some ways it does matter, right. It matters for, for metrics and for, but it also, I think, we don't have the right metrics to measure non traditional careers yet.

Lucy Collinson (00:29:42):
And, and the other aspect is that, I mean, the CRICK makes, is able to make everything that publishes open-access, which is fantastic, but really there should be a big push towards everything being open access

Peter O'Toole (00:29:56):
Which I think there is across certainly Europe and UK, I think collectively, I think it's not just a UK thing. It's a very European initiative towards that. And actually, I'm also aware that you're also quite passionate about Europe in general.

Lucy Collinson (00:30:15):
I know what's coming,

Peter O'Toole (00:30:17):
Actually. I was struggling to find the image. There you go. Probably not the one you were expecting to see.

Lucy Collinson (00:30:29):
No, but I love that. So I feel like, so that's

Peter O'Toole (00:30:33):
But what does it say on the poster?

Lucy Collinson (00:30:36):
Is says so we wonder why we never get any votes at Eurovision?

Peter O'Toole (00:30:39):
No, I think that sums you up twice over there's two important messages in this.

Lucy Collinson (00:30:44):
Yeah. I mean, I, I have a banner, I feel like I've spent the last three years going on anti Brexit marches. And I have a nice banner in my office as well saying science needs EU, science needs you. But of course, yeah, I, we do love the Eurovision. I mean, it's, it's kind of a British tradition that you have a cheesy party for Eurovision, where everybody brings food. That is a pun on the different countries that it comes from.

Peter O'Toole (00:31:15):
I wouldn't say that's Everyone, Lucy, I would say, I wouldn't say I've got to be careful how I word this.

Lucy Collinson (00:31:22):
Yeah. Be careful.

Peter O'Toole (00:31:24):
You, are you, are you a Eurovision, a fanatic? I would argue at this point,

Lucy Collinson (00:31:32):
Well, it doesn't hurt that it's around my birthday every year. So,

Peter O'Toole (00:31:36):
So this was a memorable birthday, I think.

Lucy Collinson (00:31:40):
Yeah, that was a big birthday. And the year before we had our usual Eurovision party and somebody said, well, because it's your big birthday next year. Then we should actually go to Eurovision wherever it ends up being. And it was a close call between Copenhagen and Azerbaijan. And we ended up in Copenhagen and it was, it's a great way to see European cities with a bit of cheesy music.

Peter O'Toole (00:32:06):
And am I correct in that you have a Terry Wogan dress?

Peter O'Toole (00:32:11):
Well, you might think that from our Twitter feed. So in locked down, we have, we've had lab coffees and we have a different theme every day. So of course, for, for my birthday and Eurovision, we had Eurovision theme and I didn't have a green screen. And my, my background wasn't working. So I had to hang a green dress in the background and Terry Wogan's face was, was on it because for us in the UK, Terry, Terry is Eurovision,

Lucy Collinson (00:32:43):
All hail Sir Terry,

Peter O'Toole (00:32:44):
Graham Norton's not so bad.

Lucy Collinson (00:32:46):
Oh, Graham is great as well. But you know, for Euro it's Terry,

Peter O'Toole (00:32:50):
So that's important actually. So your team obviously mean a lot to you. Obviously we saw them with hard hats earlier. But actually I looked at this photo. I think the photo I have now is of your lab. On the last day before lockdown,

Lucy Collinson (00:33:06):
I was the last kind of big lab training event. That's, you know, they're all having so much fun there. So this was in preparation for the Zeiss 3d EM and the meeting that we were holding at the CRICK supposed to hold at the CRICK in March, and we had to take the difficult decision to cancel it or postpone it. And it was before we really knew whether we were going to have to go into lockdown as well. But Zeiss had shipped an SEM on site and they were all learning how to use STEM detectors and and use the array tomography software. And they're having so much fun, kind of makes me a bit sad that I wasn't there. I don't get on a microscope very much anymore, but there's such a talented group of guys. You know, if I, if I can't get on a microscope then the fact that every week we catch up and they show me this insanely cool data and reconstructions and analysis is it makes me happy,

Peter O'Toole (00:34:04):
Which is good. And obviously this isn't your whole lab. Your lab is actually this, this cuts people out at the edges, obviously a lot larger. When you think about that, your postdoc lab and Colin Hopkins was a great scientist. Look at the lab that you had here. The size of your own lab is significant.

Lucy Collinson (00:34:20):
It is now, yeah, it is now I get in what, 2004, it was just me. And it's been a very gradual buildup over the years as the size of the Institute has grown. You need more people. And as, I guess, as you, as the technology develops, and as you show what it can do, then more people want to use it. So

Peter O'Toole (00:34:44):
I think, you know, I, again, I have a picture of you and I haven't got it downloaded for some reason, which is frustrating to know what it was going to be off. I think when I started similarly, there was myself and there's Meg who's my electron microscopy specialist and the lab grew and grew and grew. I think we were both very fortunate that our timing of coming into core facilities has been when core facilities, started to come into being, but also the technologies that we're being involved with were very much in Vogue and in fashion. And were very successful to develop, but to develop the lab you really had to. Yeah, it is very a good analogy. It is like surfing and you have to surf the wave successfully to get there. I don't have the picture of, I noticed behind you is probably from one of your holidays, Newquay or similar,

Lucy Collinson (00:35:38):
Polesworth the North coast of Cornwall. I don't know if I can pull up the, the photo

Peter O'Toole (00:35:48):
So out of work itself you know, it's a big team to manage I'm sure lockdown. That's the other side of me? Can we go sideways on it?

Lucy Collinson (00:35:58):
I'm not sure why I'm on the side. Although I have to say, when I surf, you know, I love surfing and I talk about surfing a lot and every holiday is a surfing holiday, but that gives the false impression that I can surf. And I can't, I didn't start till my early thirties and I've never been sporty. And it's not about that at all. It's just about the feeling of being in the sea and when you're getting slapped around the face from both sides, by a wave and I don't even know how that's possible, but you can't think about work. And even if there's no way to come float in the middle of the sea and you know, you've just got the sun and the, air the air smells a lot better than it does in London. And it's. Yeah. It's great. And look at, look at the view. So beautiful

Peter O'Toole (00:36:43):
And the salty water and the cold and the I'm not getting it at all. I'm just, yeah.

Lucy Collinson (00:36:51):
I mean, I just, I didn't like the sea before I started surfing and there was no way that anyone was getting me in a wetsuit because just look at them. And then one day I tried it and the first day you have a lesson, most people make some attempt at standing up and it most people get hooked. So,uwe have, we have lots of group holidays down to the North coast of Cornwall and actually there's quite a high proportion of electron microscopists on those holidays. They have to say, not surfing. Yeah. Go figure, It's because we're locked in basements most of the year in the dark. So every now and again, we get let out when we go crazy. So

Peter O'Toole (00:37:33):
Get wiped out instead of black out, I guess, on the (inaudible)

Peter O'Toole (00:37:37):
Words.

Peter O'Toole (00:37:39):
So I say back to you, so you have successfully surfed that wave career wise, but have you found actually challenged you the first picture I showed, you mentioned the Terry Wogan dress, but you've kept your lab fairly well engaged throughout lockdown I remember on Twitter actually from Martin, I think it was Martin Jones who actually tweeted this. This was a very scary image of you.

Lucy Collinson (00:38:05):
Okay. So this one, so say the idea for themes

Peter O'Toole (00:38:10):
And you're not really home alone though.

Lucy Collinson (00:38:13):
No, this one was the scream. I think it was probably like week three or week four of lockdown, and everybody was having a real dip. So,uhalf of the lab had the, the scream, the painting as a background and half of us had the home alone. Uand we were, we were doing the, the scream and then,uan unnamed person in the lab took that and ran with it literally. And,uI think that unnamed person is probably Martin, but there's now a whole Twitter feed called,uhashtag Lucy running away from things.

Peter O'Toole (00:38:48):
There's all sorts of backgrounds. I think ultimately you enjoy virtually dressing up.

Lucy Collinson (00:38:57):
Yeah. I mean, I love it. It makes me laugh. And I think if there's anything we need right now, it's having a good laugh. And again, they come up, I've been chased by the ghosts from Ghostbusters and Telly Tubbies and Giant Haystacks, the wrestler and all sorts so right. Whoever it is, I encourage them to continue.

Peter O'Toole (00:39:19):
Yeah. I think good for team morale as well. So you've obviously been doing a good job from that perspective. There was one picture that you sent me, which I was very intrigued by, which actually a picture of an airplane and the distance of you on the airplane to McDonald's for chicken nuggets.

Lucy Collinson (00:39:41):
Yeah. You might have to go the other way. See that there's a plane. Okay. Yep. So there's me on the airplane. So my brother loves airplanes and he, he follows my travels around the world, on the flight radar every now and again, not the whole time that would be weird. Right. but he, he knows which he knows which plane I'm flying on and whether it's on time. And, and it got to the point where he was texting me before, just before landing. So when I turned my phone back on, I'd have a message saying welcome to wherever. So that one is Frankfurt and I think I'd arrived quite late and he thought I might be hungry. So he's,uhe's pointed out the nearest chicken nuggets in McDonald's, which I think was the only restaurant labeled on there to be fair.

Peter O'Toole (00:40:28):
So you're not a big McDonald's fan.

Lucy Collinson (00:40:31):
Do you know that? I have been known to have a McDonald's in Frankfurt airport on the way home.

Peter O'Toole (00:40:37):
Yeah. I think I've done similar. They've also got Häagen-Dazs as well in there. So I kind of, I see their waffles there quite good. That's usually where it's actually, it's moved last year. It's moved. So I no longer get that when I go there.

Lucy Collinson (00:40:54):
The irony being we'r e both quite foodie aren't we. So we're talking about McDonald's

Peter O'Toole (00:41:04):
I'm not so fussy tho, I, I think I, I do enjoy McDonald's occasionally

Peter O'Toole (00:41:09):
Too often.

Peter O'Toole (00:41:12):
So quick fire questions then, and we're going to start with food eat in or eat out,

Lucy Collinson (00:41:18):
Ooh. It depends on the day. If it's the weekend eat out during the week.

Peter O'Toole (00:41:25):
Great. Quick fire. Answer that one, Lucy.

Lucy Collinson (00:41:28):
It was quick.

Peter O'Toole (00:41:30):
Okay. Cook or wash up.

Lucy Collinson (00:41:32):
Cook

Peter O'Toole (00:41:35):
Cook. Have you ever told Chris, that we have a friend called Chris Garin, a common friend who we both know very well. And when he ever visits, he'll always cook that that's his big thing is cooking.

Lucy Collinson (00:41:49):
I mean, he's, he's been a chef. His, his cooking is insanely good. And he came down to Polesworth with us. Last November, we took him on a nice beach holiday and we actually stayed on a place on the beach and it was gale force winds for days, the poor guy. And but he cooked us some incredible food. So always try and take Chris with you on holiday

Peter O'Toole (00:42:13):
But you'd still rather cook than wash up when he's there.

Lucy Collinson (00:42:14):
No, I'd rather he cooks.

Peter O'Toole (00:42:18):
Cause he will be listening to this. You have to be careful. Okay. Beach bum or sightseeing. Quick answer.

Lucy Collinson (00:42:28):
Well, wow. Got to say beach bum cause the surfing.

Peter O'Toole (00:42:31):
Tidy or messy,

Lucy Collinson (00:42:34):
Messy.

Peter O'Toole (00:42:35):
Tea or coffee,

Lucy Collinson (00:42:37):
Coffee

Peter O'Toole (00:42:38):
Book or TV?

Lucy Collinson (00:42:40):
TV.

Peter O'Toole (00:42:42):
Okay. Stay at home or go to work.

Lucy Collinson (00:42:45):
Oh, I don't have much choice at the moment I go, go to work. But if you'd asked me when I was at work every day, I would have said stayed at home,

Peter O'Toole (00:43:00):
But you're now say you prefer to be at work.

Lucy Collinson (00:43:03):
Yeah, I think he quite liked me out the house. Now it's been what? Three months.

Peter O'Toole (00:43:09):
So, so you miss him when you're at work and when you're at home, you obviously want away. You'll get yourself into trouble with that. So TV. So, so you prefer TV over books. I would concur with that, but so what's your, what are you into at the moment TV wise?

Lucy Collinson (00:43:27):
Well my favorite is Spooks, which if anyone hasn't seen it was a series about MI5? Not nine to five. And it was kind of, I guess it was around the time that 24 was on as well. So it was, it was very British, but it was the first one that I had that really tech feel. Uthat would be my go-to I am trying to read, but it's, I dunno, it's hard to concentrate, I think with work and with Twitter and with everything being so, so quick. And is this still a quick fire round? Cause I'm,

Peter O'Toole (00:44:06):
No No I've got you. So I've got you into trouble with the other half, so I'm quite happy to stop there. Yeah if you've got young children don't want spooks with them.

Lucy Collinson (00:44:15):
No, especially not the first episode,

Peter O'Toole (00:44:17):
Correct yes

Peter O'Toole (00:44:21):
Yes. I remember that, you know, that's one of the few vivid moments of TV I remember watching that scene and thinking, Oh my goodness, it was a big actress as well.

Lucy Collinson (00:44:29):
Yeah, well that, they were one of

Lucy Collinson (00:44:32):
The first that I remember that quite happy, killed off major characters. And did it frequently?

Peter O'Toole (00:44:38):
Yeah. Was that first episode really on a Friday could plug in there for anyone who's watched that first, first episode.

Lucy Collinson (00:44:47):
And I have to say that because we've had a couple of master students from your course and York and both of them have been really excellent punners. So, you know, you're not only teaching them microscopy, but you're also making sure that they go out into the world, able to canvas

Peter O'Toole (00:45:03):
Catherine and Charlotte, I think both came down to you didn't they? Catherine is now working for you as well.

Lucy Collinson (00:45:09):
Yeah. Catherine went over to Graham Knott's lab in Switzerland. Then we managed to get her back and she's fantastic. She's working on projects and helping Rafa with the operations. And Charlotte is now in Oxford. So she did a PhD in, in Leiden. It's one of the really nice things about science that you don't get until you're a bit,uI don't think I can say older, can I maybe later career, when you start seeing your kind of lab kids go off and do their thing and then build their careers and come back in and that's very cool.

Peter O'Toole (00:45:43):
Yeah. I, I think, I think maybe that it's not common of all core facilities we have had students come in and then carry on their career around the technology rather than again, rather than the typical academic route. And both of those students were masters students at the time. And they're meant to be trained to go into our type of roles or similar in industry. I think masters is not always commonly thought of, is it a good degree compared to a PhD, but actually it equips them really, really well. And in Charlotte's case, she's obviously gone on beyond that anyway, but they can still forge very high profile careers and specialize in that technology. So very different routes, but it still needs that high degree of expertise and specialisms just as you would in an academic career. I think you've got two excellent examples there, but, but you, you helped inspire them significantly once they went down, I think that was the London research Institute at the time that you're out.

Lucy Collinson (00:46:43):
Yeah, it was Cancer research UK. She came, they were both paired up with the postdocs in the lab with Chris and, and others so they were learning directly hands-on from some really great electron microscopists,

Peter O'Toole (00:46:58):
Which is fantastic. I'm going to just turn it back to science itself. And we've talked about where you started, where you've got to, what's the greatest challenges that lies ahead. Where's the unmet need that we need to see developed. What's going to really drive microscopy forward in your area, in the future that isn't possible today.

Lucy Collinson (00:47:20):
The automated image analysis. So that's where we're devoting a lot of our development time now. It's partly the citizen science,

Lucy Collinson (00:47:30):
It's partly deep learning. Ua lot of it is I guess, things like Neubias, which is a European network of image analysis analysts building up the career structures,uand, and producing more people to come and work in, in facilities and in research groups to develop it. Uplaces like EMBL, EBI,uEuropean bioinformatics Institute who have the public archives where we're starting to deposit our data so that,uimage,andthis and other scientists can remine it that goes to open science. Again, I think there's a huge amount that needs to be done in that area to really equip everybody, to be able to collect your big data, whatever it is, whether it's,uvolume EM or light Sheet or Spatial AMX, or x-ray microscopy, you collect it in 24 hours and 24 hours later, you have whatever you need to quantify in volume EM that's going to be 3d models of organelles or of neurons,uand some way to quantify them in other domains it might include time as well, but, and high throughput, which needs automation. So EM has never been high throughput, but you're starting to see,uof the first big data coming through fast and places like EMBL and Yannick Schwab's lab,ureally pushing that kind of high throughput work that will make the data significant as well,

Peter O'Toole (00:49:08):
Which is why I was thinking when you said about the analysis and the high-throughput analysis, as soon as that comes to be, we then need the high throughput of the data. It's where the bottlenecks exist. I guess at the moment, does he not frustrate you that deep learning can computers cannot easily render images?

Lucy Collinson (00:49:33):
It doesn't frustrate me. I think if they could, we'd have to worry a bit because we might have reached the singularity. It doesn't frustrate me. I think it's really exciting, but there's the potential that we can teach computers to do some of that heavy lifting for us. And actually we've had two sandwich students in a row,uHarry and Daniel who come from a computing background and these are undergraduates and these are the guys who are who are really doing some heavy lifting on the machine learning side. And it's just a new generation with different expertise. And when you, when you get them working across disciplines with biologists and microscopists it's really exciting,

Peter O'Toole (00:50:25):
I've got, I've got someone from maths, computer science, working as a PhD in the lab at the moment. And I guess my frustration is, I don't know the work as well as they know the work.

Peter O'Toole (00:50:39):
And so

Peter O'Toole (00:50:39):
It's hard for me to understand their bottlenecks, their problems they're encountering because conceptually it's really

Peter O'Toole (00:50:45):
Easy, but

Peter O'Toole (00:50:47):
Obviously it's not because no one's solved it. And I guess I feel add to my depth or inadequate in my knowledge base, not I can't advise them particularly well. We've got obviously another supervisor who's expert in that area. I think that side frustrates me too maybe more frustration of myself that I expect great things, and I think it should be easy to solve. And I appreciate it isn't

Peter O'Toole (00:51:13):
You should be,

Lucy Collinson (00:51:16):
Need to translator as well as, you know, running the research programs in microscopy prototyping. Martin is basically my translator for hardware, software, design engineering, machine learning, and it's fiendishly difficult. It can take years to not learn another topic, but learn how to communicate with somebody on that other topic. And he's extremely patient he's, you know, he's a person he's got me Twitter enabled, and I even know what a Jupiter notebook is now. And I've done a kind of zero to hero phython training, which is fantastic course, if anybody wants to do it but I'm never going to be an expert in coding. You just need, need to know enough that you can communicate and you all need to, you know, bring your expertise to bear, to get to what you need for the research.

Peter O'Toole (00:52:12):
I think that's very good advice actually. And I completely agree. And actually my students and the Judy Wilson who are collaborate over in maths are very patient with ourselves and they do explain things very clearly. It's just, when I leave the meeting, I lose some of that information. I think they have to keep me teaching me quite often, please just not instinctive to me at all.

Lucy Collinson (00:52:38):
That's very diff different. Somebody explaining something simply to you and you understanding it. That's very different to being able to then go and explain it to somebody else in the same way.

Peter O'Toole (00:52:49):
I think the tolerance goes both ways because we have to explain what is quite simple to us as, as they're not biologists, not microscopists hardcore. Again, I think, I think it goes both ways.

Lucy Collinson (00:53:02):
Yep. And biology is messy, right? Yeah. Alot messier than physics and maths. And that's, I think the thing that people from the other side have to get to grips with.

Peter O'Toole (00:53:13):
Yeah and chemistry also. Yeah. I guess if you add A, to B you get C and it's repeatable whereas in biology the heterogeneity

Peter O'Toole (00:53:26):
Means that you will never get the same result twice. Yep. Trends, but not the same. Well, look, think about your nuclei. Not, they're never going to look the same. Are they? Each one is going to be completely unique, even if it's in the same cell type. In fact, the same cell seconds later will be different.

Lucy Collinson (00:53:45):
Yeah. only need a lot of data to start spotting the patterns

Peter O'Toole (00:53:50):
Heterogeneity does make biology very, very difficult and why it's so expensive.

Lucy Collinson (00:53:55):
Yeah. But it's, you know, it's a problem that's been overcome largely in the Omix. It's just the imaging isn't there yet.

Peter O'Toole (00:54:05):
No, but I guess it's the Omix and coupling to that, that's a big route forward as well in the future. So before we finish off, I'd like to ask you about, what's been the best time of your career. What, what period of your career have you most enjoyed?

Lucy Collinson (00:54:26):
I think, I think now, because

Lucy Collinson (00:54:33):
It's such a good job, Pete, I think, you know, for a long time, it's a struggle because everybody seems to know everything and you don't know everything and you think that you should know everything and it's only once you've done it for 20 years or more, and you've collaborated with people and you've picked up stuff from different subject areas. And it's only when you learn all of the stuff, especially in biology, that, that it starts to all come together. And you can, you suddenly realize that your you're there and you, you know, what's missing in your field and you know, what you want to do with it. And you can have conversations with different people in biology or in maths. So in computing, in physics. And I think for me, the fun bit is when you, when you see the data that the guys in the lab are collecting, but when you have that network and you can start putting together really big scale ideas that could really make a difference to science on a, a much bigger level.

Peter O'Toole (00:55:39):
So I guess all that comes with confidence.

Lucy Collinson (00:55:42):
Yeah. Which takes a long time to build up.

Peter O'Toole (00:55:45):
And how confident are, you know, when you do your, when your invited to give a keynote, a plenary talk at a big conference, just don't get nervous or, you know, a lot more relaxed and confident

Lucy Collinson (00:55:57):
A little bit, but tho, you know, yeah. I used to feel sick for a week before a talk when I was doing my PhD and my postdoc and for a long time. And now it's, it's one of the things that I enjoy the most actually. And,uI think stuff, if you don't, if, if it makes you nervous or you don't enjoy it, you just have to keep doing it and eventually you get better at it. And then you get a bit confidence,

Peter O'Toole (00:56:24):
I guess a lot of people always worry. There's people in the audience to know more than you know about the subject or might ask a difficult question, but I don't think I've ever encountered a really going to set myself up now for the next time I give a webinar or a conference. I don't think I've ever had a really difficult question that I should have known the answer to, but didn't know the answer to, so I think it's fine not to know the answer to a question. And just to say, I'm not the expert there and ask the audience or come back and I'll find the answer out. Yep.

Lucy Collinson (00:56:56):
It's okay. Not to know. As long as you say you don't know, you only get into trouble if you start to wing it and make it up, because there will be somebody in the audience who does know you can, you can bet on that.

Peter O'Toole (00:57:11):
Yeah. No better in this very specific area, but probably for the whole content of the talk. Probably not. Yeah.

Lucy Collinson (00:57:20):
It's like when you do your, your Viva or your thesis viva, right. You're, you're the person who knows that work best.

Peter O'Toole (00:57:28):
So, okay. Just some slight bits, some of the pros, some of the perks maybe of the job. So you sent me through this picture, which is of you talking to Sadiq Khan, is it, the Mayor of London.

Lucy Collinson (00:57:45):
It's about to take part in our citizen science project. So the screen on the left, just above your head has extra sun on it. That was the beginning of London tech week. And he was fantastic. He didn't have long at the CRICK, but he came over to the screen and he actually, he segmented and an entire nuclear envelope in, in one of the images.

Peter O'Toole (00:58:05):
So is he say co-authored or acknowledged on the publication when it comes out?

Lucy Collinson (00:58:09):
Well have we have our volunteers as co-authors, so there's I think they're called Zooniverse volunteers in the author list. And then it will point towards a list of everybody who's contributed on the project. So it was really important to acknowledge everybody. Again, it's very non traditional science.

Peter O'Toole (00:58:30):
So he's going to be acknowledged. You're going to have Sadiq Khan as a, co-author

Lucy Collinson (00:58:35):
Not specifically, he should be in the list with all of the other volunteers.

Peter O'Toole (00:58:39):
Okay. This one, which is now you with the queen, tell me you got her to do it and you can co-author. You can put her in the list as well. Go on.

Lucy Collinson (00:58:50):
We didn't know. No that was before the citizen science project launched. I think so that was the opening, the official opening of the CRICK. And my name got drawn out of the hat to be one of the people who, who met her in person and introduced her to other people. And I just love that we've coordinated our dresses there.

Peter O'Toole (00:59:11):
I was thinking, so you met Sadiq Khan, you've met the queen. I think you gave a big new scientist talk, I believe

Peter O'Toole (00:59:20):
As well,

Peter O'Toole (00:59:22):
Do all these gigs. So that means you get to buy dresses. How often?

Lucy Collinson (00:59:28):
Well, you know, like shopping,

Peter O'Toole (00:59:33):
But not at the moment, Obviously,

Lucy Collinson (00:59:35):
I mean, this is, this is the most dressed up I've been for three months. I have to be honest,

Peter O'Toole (00:59:41):
Except for virtually, in which point you've been dressed up in all sorts of different outfits. Yeah. That was the virtual side. I say, we're coming towards the end though. So I'm going to ask one last question. Any advice that you would give to someone starting out in their career?

Lucy Collinson (00:59:59):
Another good question. I think follow what you enjoy doing. I mean, nobody, nobody in primary school says I want to be an electron microscopist, do they?. I got, I mean, maybe they do now. Right. Maybe, they know about it because of Etch a cell.

Peter O'Toole (01:00:21):
The syllabus

Lucy Collinson (01:00:25):
A bit of teaching of teachers. But I think do what you do, what you find really interesting and, and you're passionate about, and it may be that you, you only know a little bit of that. So at school I liked biology. So I did a biology degree and then I liked the biology degree and I quite liked small things. So I did microbiology for my PhD and I, there wasn't a grand plan. And I didn't know where things were going to lead. You have to develop a gut feeling for which opportunities you should take and who are good people to collaborate with. So, and don't feel like you should know everything too early on. You have to spend a lot of time in science learning before you get to the point where you can really know what you want to do.

Peter O'Toole (01:01:10):
I think that's sound advice. It's, it's just following what you're good at and the opportunities, again, back to surfing, I guess, back to sooner than later.

Lucy Collinson (01:01:20):
Yeah. Don't worry about the failures as well. You will fail as part of your career and you will fail to stand up on a surf board, but it doesn't mean that, you know, you learn from it. This is very deep, isn't it learn from it. And I think it makes you a bit more chilled.

Peter O'Toole (01:01:37):
Okay. I'm going to caveat what you just said there before we end, because if your true surfing skills are what you say, they are pretty useless. Yeah. Career wise, it might be better to find a different hobby from a career perspective, fall off. If you keep falling off the same circle, maybe, maybe at times choose a different career path.

Lucy Collinson (01:01:58):
That's why we only surf places that are shallow with a sandy bottom.

Peter O'Toole (01:02:04):
And on that note, Lucy, thank you so much for joining me today. It's been a, I would say enlightening, but that would suggest lights and it's a bit electronifying. Maybe it would be a better,

Lucy Collinson (01:02:17):
I'm going to put that phrase in my next grant application.

Peter O'Toole (01:02:21):
Cool, Lucy. Thank you.

Intro/Outro (01:02:25):
Thank you for listening to The Microscopists, a Bitesize Bio podcast, sponsored by Zeiss Microscopy. To view all audio and video recordings from this series, please visit Bitesizebio.com/the-microscopists.