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Intro/Outro (00:00:02):
Welcome to The Microscopists, a Bitesize Bio podcast hosted by Peter O'Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O'Toole (00:00:18):
Today on The Microscopists I'm joined by Jan Ellenberg Head of Cell Biology and Biophysics units at EMBL and revealing, I'm really engaging chat. We discuss all sorts, including unexpected budgets.

Jan Ellenberg (00:00:33):
And then I said, how about a confocal microscope? I thought this is never gonna happen. And he said, how much it's not? And we had just talked about it. And I said, that's 400,000. And he said, could you order this this week,

Peter O'Toole (00:00:47):
The role of E M B L in kickstarting scientist careers.

Jan Ellenberg (00:00:52):
And that means it's for young people, it's for people to start their careers. It's for people to build the first labs for people to develop something new. And so you are surrounded by young international motivated people.

Peter O'Toole (00:01:05):
His special Japanese cooking knife.

Jan Ellenberg (00:01:08):
That's that's what my wife often says. I just have to give you a sharp Japanese knife and immediately you're smiling when you got home, even if the day has been really stressful

Peter O'Toole (00:01:17):
And the mutual support between service and research staff, at EMBL.

Jan Ellenberg (00:01:23):
So there's no no distinction between these two career options. And it really depends on what people are good at and also what they, what they want to do

Peter O'Toole (00:01:32):
All in this episode of The Microscopists. Hi, I'm Peter O'Toole from the University of York and today on The Microscopists, I'm joined by Jan Ellenberg from EMBL over in Heidelberg . Jan how are you today?

Jan Ellenberg (00:01:55):
I'm fine. How are your Pete

Peter O'Toole (00:01:58):
Thank you for agreeing to talk today. There's quite a lot to talk about actually, but I where's the best place to start. Probably you're very famous for your microscopy and your impacts to societal microscopy through Euro Bioimaging, but would you class yourself in the early days as a microscopist?

Jan Ellenberg (00:02:20):
I guess it depends on what you mean by early days. I mean, my, my first training and research was not microscopy. I was trained as a, as a biochemist and molecular biologist in plant biology, actually. So I only got into microscopy a bit by accident at the very end of my, what Germany has at the time was called the diploma degree. So that's your first independent research project for senior master's project. And at the very end of that gene, I had cloned and characterized as a protein, had to be localized in the plant tissue where it's expressed. And for that, I needed to use something called dark-field microscopy. And so before I had only looked at jets and fans and to expect the things. And then that was the one bit where I looked in, where was this bloody thing in the organism that I had learned it from? And I think that just made me fall in love with actually seeing, you know, the context of, of where things are. And so then I decided for my PhD that I wanted to do something with microscopy. Yeah. So, but my, my basic training wasn't at all in microscopy or physics.

Peter O'Toole (00:03:25):
So where, where was that first degree? Was that in Hamburg?

Jan Ellenberg (00:03:27):
No, I studied at Hamburg but then the first degree came from Berlin. So I moved to a private research Institute in Berlin to do this first independent research because the lab conditions were just spectacular. And so that came from Berlin, but then actually the first microscopy was in a collaboration of the Berlin Institute with the Max Planck in Cologne. So at the time the famous plant people were all the Max Planck for breeding research and cologne. And there was one guy who had actually mastered the technique of looking at Insitu RNA hybrid positions by microscopy, which was a very difficult thing at the time. So it's what you had to work in complete darkness with silver immersions to detect the tiny bit of radioactive RNA that you had labeled in a plant tissue and see where it was.

Peter O'Toole (00:04:19):
So what was your first microscope that you used

Jan Ellenberg (00:04:22):
Where that microscope was, what the Zeiss Axio, but just a plain film, dark field microscope. So I would say, yeah, that probably qualifies as the first real microscope that I used. But then the first instrument I used really heavily was, was the one during my PhD. And that was a confocal, it happened to be a Zeiss again, it was a Zeiss 410 confocal series that had just come up and was another of these accidents. I mean, that's actually a fun story to tell. I mean, I, I I started my PhD again doing biochemistry because that's what I knew I was trained in. And, and, and so I started, I mean, you know, I did my PhD at the, at the NIH with, with Jennifer Lippincott-Schwartz. She was working on membrane traffic. And so the idea was to do subcellular fractionation and, and isolate organelles. So it was all again by chemistry, grinding, upsets, you know, looking at bands, some gels, radioactive, labeling all of that. And but the year I started TFP was cloned and published. And then Jennifer said, oh, let's, you know, let's try to stick this on membrane proteins. We might be able to see membrane proteins moving like the cytoskeleton people that have been able to do this purified for us to deliver protein and re-injecting that into cells. And so I was good at molecular biology, so I did some constructs and, and then we started to do some imaging and B again, had a very simple epifluorescence Zeiss Axiophot and it was completely unusable for live imaging, of course. And and then there was one person on campus who ran NIH imaging facility, Carolyn Smith. And, and she said, you know, you should use a confocal microscope and then everybody at the time believed in, you cannot use confocals for live imaging because they use lasers and the cell would die, and then they would immediately have disaster. But, you know, we said, okay, you know, then there was another person on campus who was doing a lot of life imaging for dyes to live a membranes, like dyes and [inaudible], and he said the same. He knew you should use a for, this is actually good for live imaging. So I said, all right, you know, let's, let's give that a shot. And it worked much better than the Axiophot that, that we had in Jennifer's lab, but of course confocals at that time were really expensive. There was one in the NIH imaging facility, and that was it. And that was, you could only get to it very rarely. And it was really difficult to, to get on it, but it was NIH under the Clinton administration. And so they, they got these guaranteed budget increases every year. And so that meant at the end of the financial year in the fall, the chief of the branch would go through the labs and ask people what they wanted from the budget. And I had just been there for three months as a, as a student and to, but at NIH there were no students. So I was treated as a postdoc because they didn't actually have a PhD program. And so the head of our branch came by and said, you know, you need anything expensive. We'd have to spend the budget this year. And I said, and you know, the most expensive thing I could think of at that time of my career was, you know, I was doing these subcellular fractionations. And I said, you know, the ultracentrifuge needs a new swing out start, good roto. And and you know, maybe we could buy that. And then he said, how much is it? And I, you're probably 20,000, you know, something like that. It was a fancy ultracentrifuge. And he said, you know, we can buy that any week. Do you have anything expensive that you need to? And then I said, we had just been testing this confocal for the first time. And I said, how about a confocal microscope? I thought, okay, this is never going to happen. And, and he said, how much is that? And we had just talked about it. I said, that's 400,000. And he said, could you order this this week? And I said, all right, that's okay, we'll do that. And so that's how Jennifer's lab got the first confocal, because we just got it from that bit of budget that was left at the NIH at the end of the financial year.

Peter O'Toole (00:08:13):
That's quite an extraordinary story,

Jan Ellenberg (00:08:16):
It was really, you know, then I ended up doing the whole PhD on that microscope, which got delivered three months later. So the end of the financial years, September in the US and then that's when they always get into these budget government shutdown discussions. And the system was delivered three months later, just before Christmas. And it was one of the only, every five-year snowstorms in Washington DC. So that the system sat outside the building in the snow covered in snow, on the delivery crates for four weeks before NIH opened again, because if a shutdown because of snowfall, but it survived, it was, everything was fine now. So I became kind of attached to that microscope

Peter O'Toole (00:08:56):
And arguably one of the first Cryo stages then for it

Jan Ellenberg (00:09:01):
The first four weeks of its existance. Yeah, it was fortunately, it was very wrapped in plastic, so it wasn't completely soaked through. We finally could unwrap it and set it up.

Peter O'Toole (00:09:12):
So I think actually the first, the first confocal, not the first confocal that was back in the Bio-Rad days, my first Zeiss confocal that I used was actually yours at EMBL and one of the trips and yeah, that, that leaves. So I remember doing frat.

Jan Ellenberg (00:09:29):
Yeah. That one was set up to do that yet. So the one I then set up here was the next generation was the 510 series. Then I sort of configured it for live imagining and together with Zeiss was a bit of a custom model.

Peter O'Toole (00:09:44):
Yeah. That's and I went off and played with Rainer Pepperkok and Timmo Zimmerman, Leica SP2, which also doing frats. So it was really interesting to compare. And actually, I really loved both of the confocals. They were really quite wonderful. So you went, obviously you did Berlin and then over to the NIH, to the U S how did you find that, that move, that change?

Jan Ellenberg (00:10:08):
But it was challenging, I guess, you know, it's always a bit challenging to change country and culture. I think that always takes some time. And I, you know, like many scientists, I also was a bit of an introverted person, but the, I think the big challenge was that Jennifer had said, you know, just come over, you know, this is great. You know, you can work in my lab. And I told her I was a student and she just didn't care that NIH didn't have a PhD program. And that there was actually, there was no way to do a PhD at NIH. They did not even have a collaboration with the University of Maryland or anything, which they have now, but at the time they were just no PhD students, you know, you had more than 10,000 people on campus doing biomedical research, but not senior PhD student. So I got there and then I realized, actually, I can't do my PhD at NIH. So I had to convince people back in Berlin, by I had done my previous degree to, to supervise this from abroad and to, but, and that was fine. That was just a bit of organization, a challenge. But then at NIH, there were no students, there was no training. There was also a very, you know, American post-doc professional research culture that you didn't even touch pipette men in a collaboration before it was negotiated on which part of the paper, your name would appeal. And and so it, wasn't very different culture from what I was used to as a, as a junior undergrad student in, in, in German live science. Yeah. And so just getting into this okay. You know, forget about your PhD. I'm a postdoc now, and I have to function like one that took a bit of time to get into, to just say, okay, you know, that's how it is. It's still a great lab. It's a great project. So I'm just going to have to teach myself how to do these things. And, and I think that was a, of a shock because I wasn't expecting it, but it turned out to work really well. Yeah. Because then you just learn to do everything yourself. And so I think that that was a really good experience. And I think also the expense of the very different cultures between at the time, especially between the NIH was extremely, extremely well funded. And I was for German standards at a really well-funded Institute, but it was still an environment where you did everything yourself, you did all your reagents yourself, you would cast you on jets you would do your own preparations. You would do your own PCR mix because you wanted to make sure it's actually right. And then it has all the right concentrations. And at NH you've just bought whatever you could buy you bought, because there was so much money that you would not waste time on anything doing anything yourself that that could be commercialized. Yeah. So it was also a very different approach to getting stuff done and not worrying about how to do it, but rather about getting a result as quickly as possible. Yeah. So I think I learnt a huge amount and much more than, than I expected to, but adaptation.

Peter O'Toole (00:12:59):
Yeah. So I'm going to ask now, Jennifer was one of the first guests actually on, on the podcast series. What was she like? She talks about how wonderful research is about what is she like as a supervisor, as a boss.

Jan Ellenberg (00:13:13):
She's great. I mean, she really is. I mean, she's been on the series and I think people can basically imagine her looking 25 years younger, but otherwise being exactly the same person. I mean, she, she, she is amazing. And also that she doesn't change. I mean, in her boundless enthusiasm in 2004 for science and just in exhaustively creativity. And, and so I think she's incredibly inspiring, incredibly motivating to people in that up. It is if you're a junior and I was just starting my PhD, the onslaught of creativity you get from her, it's also something you have to learn to handle because she would generate ideas for 10 PhD projects every day. And they will be different every day, yet the things that she's suggesting to you, and of course, you know, each of these projects could last for years. So at some point you have to decide what to do and stick with it for some time. And so also this process of, of enjoying that, that there's always new ideas and always new things to think about. And that nevertheless, you know, you've got to work on something to finish anything and and see what is working and also if it's hard to pursue it. So I think that also for me was just a really good experience, but she's, she's great. I mean, really always support us, always positive, always convinced that it will work, that you will find something interesting. And I really, I couldn't have wished for anyone better. I think

Peter O'Toole (00:14:41):
I, I won't tell him, Jennifer, that you said that she looks 25 years older than she did.

Jan Ellenberg (00:14:47):
No. I mean, she's, she character hasn't changed off because she looks a bit older now, but, but at that time pumps off how she is and how excited she is about science and how much she inspires people to engage in research and, and, and pursue science. I think that was already like that. And it's still like that. And it's, it's, I think a quantity where she's really exceptional.

Peter O'Toole (00:15:10):
How many years were you? How many years were you out in the US for?

Jan Ellenberg (00:15:14):
I was there four and a half years. Yeah. So I, I spent four years completing the PhD and then I stayed six months on a bridging postdoc before I started at EMBL. So it was just to finish the project and then started it up here in, Heidelberg

Peter O'Toole (00:15:29):
And which country is best to work in Germany or the US

Jan Ellenberg (00:15:33):
Well, I mean, I'm kind of not working in Germany at the moment at EMBL. I mean, the it's, it's a bubble in south Germany it's. It's a very, it's a different culture. It really is not a German institution also in, in the way it runs. So I would say EMBL is again a different thing between Germany and the US, I would say they both have strengths and weaknesses. So I think it's really, it really depends a little bit on what kind of project you're working on and maybe also in what phase of your career you're working in the system. So I think for early stage, researchers in my experience in the US was amazing. I mean, the, the environment you had, the productivity you had, the ability to get stuff done quickly was incredible, but there was also a very high pressure to produce results and, and to finish things and so forth, junior statutory such, that's fine. You anyway, don't have such big long projects and and having to apply for money all the time and getting that in changing projects is, is what you do anyway. But I think for longer term more sustained projects, that there may be some weaknesses in the US system that that's harder to do. You know, that if you have to work on something that takes five, 10 years before it really comes to fruition, I think that's more difficult to support in the US system. It's not impossible, but it's, it's, it's more difficult to support. And I think that it's easy in the German system, because then two senior people, they make these very long-term commitments and they also have very long-term in tomorrow funding. So I think this may be a bit of a question when in your career, are you in which system, and also what type of work are you engaged in where the support is maybe more easy or harder in one or the other system to get?

Peter O'Toole (00:17:18):
So did you go over to the US by yourself?

Jan Ellenberg (00:17:23):
I did with my partner at the time. So, so we, we were two, two scientists. And that was part of the reason we ended up at NIH because it's so big and there are opportunities for very different scientists. And then to my partner at the time, she was a structural biologist. So rather different area of research. And it was easy for both of us to have jobs there, but actually we scanned kind of the east coast. So we interviewed in lots of places, we set it up on NIH

Peter O'Toole (00:17:52):
Over the east coast,

Jan Ellenberg (00:17:54):
Only the East coast Yeah. Yeah. So that yeah, for some reason, I guess we, we were students, we had to set and organized all of these things. We also didn't come from rich families, so we could essentially afford one trip of interviews. And then there were more connections. We had two labs on the east coast. So we just did it on that side of the US

Peter O'Toole (00:18:15):
You touched on, you already touched on the EMBL. Is is not part of Germany. It's very different. So actually for, for those that are not aware of EMBL European Molecular Biology Labs, would you just briefly describe what EMBL is and the concept of it?

Jan Ellenberg (00:18:31):
Sure, sure. I, I won't do the whole EMBL introduction, but just in a nutshell, I mean, so EMBL is the entire governmental European organization for molecular biology. It's now over 45 years old. And so it's owned and run and funded by, by now, 27 member states. So it's really an intergovernmental research unit. And most similar that many people know from physics is sun. So it's created by all those countries to do frontline research in molecular biology, but also to, to services and technology development in molecular biology. So it's not just doing research, it's also providing services for the research community in all those countries. And so that means it's, it is on that choice, really centered around research centered around technology development and services for research. And so the whole organization is set up just for that and has its own rules to operate just for that purpose, because it's like NATO or like the United nations, it's an entity that governs itself. And so that means it's very international. The staff is extremely international, but also all the rules and procedures in the organization are there to support the research mission. And so that makes it work in a very different way than, than traditional organizations that are often part of universities or part of health ministries or organizations that have other additional emissions that, that make running them a bit more complicated. And I think the other thing that is unique about EMBL is it's turnover system. So people don't stay here with some exceptions and I'm one of them. So I'm not very representative, but we have for 90% of our staff, we have a maximum duration of staying here of nine years. And so for students it's four, for postdocs it's five and for faculty it's nine, and then people go, and that means it's for young people, it's for people to start their careers. It's for people to build the first labs for people to develop something new. And so you are surrounded by young international motivated people that are only here for some time to do something special and then move on in their career and then go to a national system. And so that makes it also a very different environment, because all the support we give to the research given to the young people, it's given to the juniors, the young groups to the starting groups, they get all the technology, they get all the investment, they get the new students, new postdocs and all of that. So it's, it's a place made for young new talent. And that again is often different in more traditional university-based systems that people stay longer. And then people tend to build hierarchies and big labs and things like that. So, so here is these kinds of things don't really happen. So I think that's, it's an amazing environment. And also in terms of the interdisciplinarity and the collaborative nature of it, I've never seen anything like it. It's because there's no competition for resources because it's very bottom up. And each group leader is completely in charge of what they do research on. They're extremely free and everyone has the same resources and everything is shared the incentive to collaboration and doing things across discipline is extremely strong. And it's just naturally everyone collaborates. And so for me, that just turned out to be a good fit. I like to do interdisciplinary stuff and not do everything myself. So it's, it's an amazing environment. So I can only recommend it for everyone listening to, to consider their career.

Peter O'Toole (00:22:02):
It sounds idyllic. It sounds like every research community should be like that, but obviously it can't because you need, you need homes, ultimately integrate catapult resource and you're right. People get there, they establish their name, they go off and then take that experience and the network as well to other places. So it filters through which, which gives much broader benefits in that case. And you mentioned that, you know, they go with, they build them bigger groups. I would argue that you're one of the exceptions at EMBL. First visit was 2001, I think it was. So you were only there a couple of years and already recognized this really big, exciting scientist at EMBL. So I remember listening to you talking to you using the microscope, and you were already seen as a, as a, as a future, but your group there is also really big. So actually you've done what very few people have done and actually established quite a large group at EMBL at how many, how many people did your lab at the moment? Yeah,

Jan Ellenberg (00:23:06):
So we are actually shrinking at the moment because one reason why we grew quite a bit is that we had two very large European community support the technology development projects to establish high throughput methods of microscopy, to, to apply microscopy, to all mix scaled science and, and that these were sort of self-contained projects, but they required so much technology development that essentially I had to start a second group to be able to do that. So, so driven by those projects for 10 years, I had to defacto second group that I was supervising, but it was still all run under my name that made the group look much bigger than normal EMBL groups, but those projects are completed. And so we actually shrinking at the moment. So yeah, so we are in the lab. Really. We are, we are now around 15 people at which still for,, that's still a lot for one five. So that's, that's new for EMBL a big group, but it isn't, we, we had a time when we were more than 20, and that really is very unusual for you that it was driven by, by these big U projects that we run and they were successful, but now they are completed. And then also I've been rather engaged, as you mentioned earlier in building infrastructure projects. And so the commitment I made to Euro Bioimaging and now more recently, the EMBL imaging center that just also precluded me from running such big project on the site.

Peter O'Toole (00:24:34):
What would you say your management style is?

Jan Ellenberg (00:24:38):
Well, I guess you should ask people. I manage, I would say you know, a combination of, of lead by example and, and give people as much responsibility as they can take. So, so I really I'd rather avoid micromanagement. That's really hands-off. I think it's, it's about making clear to people what you expect of them and, and trying to make them responsible for what they do, and also build them into the project design and into what the job is so that they, they take it as their role. And as, as their responsibility, whether it's a management project or a research project, I think people are only really good and creative if they own something. And if they really feel, this is my thing, you know, I want to make this succeed. So that's what I try to do for everyone that I supervise that we design what they do in the role in my group in a way that they are really part of that. And, and then, you know, even for junior people, I try to always tell them, you know, you can come to me for advice anytime, and I'm happy to design also the details with you, but if you can do it by yourself, you do it. Absolutely. You know, that's, your job is to become independent. And the earlier you learn how to do that, the better. And so I really try to give them a lot of responsibility, not too much so that if they are too junior, that they don't crumble on that and then take it too serious. Or maybe if you left alone, but you know, constantly balancing that yeah. That, that really people should run as soon as they can and, and take things to their own heart and, and, and go with it because that's here at EMBL. Again, we're here to train people for a short time and then they should move on and become independent. And so it's not useful to micromanage them. And then they leave this environment and they can't function on their own. They must become independent. And some people take more guidance to be able to do that. And others are essentially ready when they come in and you just have to agree on what they should do it, they go for it. So I would say, you know, as hands-off as can be, but it's very individual, people are different and you can't do the same with everyone. Yeah. So this, you have to talk to everyone and learn how people work and where they need support and where they don't need support. And that's a new discovery with every person you work with.

Peter O'Toole (00:27:00):
I, so obviously that brings in different challenges, different excitement, different challenges throughout your career, what period has been the most challenging for you and why?

Jan Ellenberg (00:27:12):
Yeah, I would say, I mean, there's been a number of them. I would say we talked a little bit about the culture shock at NIH when I started my PhD. But I would say that that certainly wasn't the most difficult. It was unexpected. And then adaptation, but after half a year, it was fine. I think when I started this serious political work in Europe, I mentioned to to create something that, you know, not just scientists need to support, but, but also politicians and governments need to support. And where potentially a lot of money is involved because of that. That was something that took me quite some time to adapt to. Because, because as a scientist, you are really trained to make rational arguments. You're trying to convince people by logic and do this. The more senior you get in research, you are really good at that. You can make your case, you know, you can build the logic, you can maybe make it a Peck of it on a textbook. And if you do that, then in science that works, people will say, yes, you're right. You know, let's do it like that. That's not how it works in politics at all. I mean, you can make the best possible rational case and people will still not at all the interest at or say, you know, I don't care whether you have a good case or not. That's not why I'm going to support you. And and so you have to understand how this system works. You know, what are the reasons for people to engage in something and how do you work with them? And how do you convince them that this is nevertheless a good cause and that this is something that they should be supporting and that they will also benefit from, even if the benefit is a different one than the main one that you maybe see as a, as a researcher. And so I think that I had not expected that to be so fundamentally different to, to argue, and that you can't get anywhere with logical, rational arguments with some of the people you need to work with, it's not because they're stupid either. They are not, but they have different priorities and they function in a different system and you need to understand that and also need to understand their agendas. And so I think that took me much longer than I had thought. And that was sometimes very difficult because some of these negotiations can be really tough and people can get very personal in their negotiation tactics. And that's, again, something in science that happens relatively rarely that people attack you personally, because that's just part of how you negotiate, but in politics, that's relatively common. And so you have to get used to that. Yeah. That, that, that's just part of the game. And that took me some time. I'm, I'm, I'm not someone who likes to fight in public. And that's just part of what you have to do.

Peter O'Toole (00:29:42):
How frustrating was the communication, what tactics have you developed to, to make the communication to politicians better? How'd you convince them, it's still, you still got to get them on side. How'd you do? How frustrating was it? And then how do you convince a politician of what is rationally correct, but they're not seeing it.

Jan Ellenberg (00:30:05):
Yeah. So it's two questions. So I think it was very frustrating. I mean, it took, it took quite some time. I mean, we we took 10 years to really create Euro Bioimaging and building the science case and the scientific community around it, I think was also a lot of work, but actually it was very enjoyable. I mean, the community, it's a great community, it's a fantastically supportive community, and everybody wanted to do this. Everybody wanted to collaborate. Everybody wanted to share resources to create better infrastructures and to move the technology ahead for the community. So there, you know, you just had to organize it, which was difficult because the community is so big, but the goals were easy to agree on for, for everyone to support. So that's that I think was very enjoyable. The political case was very frustrating because that took most of that 10 years. So I would say the science case took maybe three of these 10 years. And I would say seven of the years, we spent on getting the political case done and dusted, and then also created as a long term new legal entity under European law. I would say that's been the most difficult publication of my life to have the statutes of the Euro Bioimaging published in the official journal of the European union as a legal text that came out. I almost cried, which I normally don't do when we publish something. But this, this was 10 years of work and it, it made it, but that was really hard. And I would say the, the secret is to understand what people really want. And in politics, that's often not communicated on the surface. So, so people, will do all kinds of negotiation, tactics, and smokescreens behind smokescreens and smokescreens and build up threats and build up a case to negotiate. But then what they actually want only comes after you've been through all that end to end after you've had your fights enough that you have established mutual trust. And after they have learned that they need to respect you because you will not give in easily. And then you can finally talk to them and say, what do you actually want? And then often something completely unexpected comes up where you think, oh my God, if I had known that from the beginning, we would have saved two years of time. And and it's just that people don't tell you, you know, they first go through these rituals that they have in terms of establishing trust, establishing respect, getting something for their pet projects out of it, even if it's completely unrelated. And then once you've done all of that, then you, you know, you sit down after dinner, somewhere over a beer and you ask them, okay, now we've gone through all of this, you know, and we, you know, we know each other, we know life can be tough, but in the end we are all trying to do a good job. You know, what do you actually need to sign this? And, and then often very unexpected things come out that, that sometimes are really hard to fulfill, but sometimes also really easy to fulfill in that if you just didn't tell you what they wanted. So I think in the end, it's very simple. It's about establishing respect and trust with the people you negotiate with because almost never are they badly intended sometimes they are. Yeah. But, but I would say it's even in politics, that's the exception, but often the agenda and the mission is just fundamentally different and it's not transparent. So you just don't know that. And, and getting to that core and understanding that is what takes time, because they will not easily volunteer that information. It's, it's too confidential and too political sometimes. Yeah. And so that, that I think is was the most challenging to, to learn how to win the trust of people that actually don't trust you. And that think also you are threatening them and then get around that and never that has worked together.

Peter O'Toole (00:33:58):
But these are politicians I presume at this point that we're talking about how personal were their attack?

Jan Ellenberg (00:34:05):
Well, I mean, people called my boss said Iain and said to you that you should fire this person. And these were so, I mean, they did it, there were things like that. You know,

Peter O'Toole (00:34:14):
Why, why, why, why, what is it? It's so offensive.

Jan Ellenberg (00:34:18):
Like the project, the project was in competition with other projects and other projects were the ones that they wanted to succeed for political reasons, for purely political reasons. And there's always a selection between different infrastructure projects. And so if you come with a strong project and which it was from the beginning, but it's in competition with something else that is weaker and that you are not intending to compete with, but just by the nature of how European infrastructure has been, not all of the projects can go through. So the good ones we go through and the ones that have a strong political case. And so people will sometimes just because they have invested in another project that they are more interested in, they will try to stop yours. And they would try to at all costs because relatively large sums of national investments can be involved to support that. And so they, they go to, I had, you know, really things where you think, okay, that's not okay. You know, you can't just call up my boss and, you know, do personal threats and things like that know that that's not at least not how I play the game often in research. I mean, it's competitive, right? But you compete about who has the best data and who has the best argument and the best logic. You're not trying to personal threats to, to hold people back from doing something

Peter O'Toole (00:35:37):
I am shocked and have appreciation of that side and [inaudible]. How do you cope with the stress of all that? Because that must be hugely stressful and just, I know upsetting, actually

Jan Ellenberg (00:35:50):
It is upsetting. I mean, you have to get used to it. I mean, this is also, you know, I worked with a team of people here at EMBL on this project, Euro Bioimaging and it wasn't an amazing team and really a lot of the credit of pushing the through goes to them, not to me. And I also had the backing of my organization, you know, this was something that EMBL wanted to do. And so it was clear that I was working in line with EMBL's mission and that I was covered here, but this was part of my professional duty. It wasn't the appropriate person, a thing at all. It was just something I wanted to do. Right. Because EMBL had asked me to do it. And it's you know, when I do something professionally, I tried to make it succeed. So it wasn't my personal pleasure to engage in this. But, but it became because it's a big project, it becomes threatening to some people. And so this I had to develop this, what I always told the Euro Bioimaging team, you know, you have to have Teflon when you go into these negotiations, you never take anything that people say in negotiations personnel. You know, because then you kill yourself. If you ever take this person that it's gets so bad sometimes. And so ugly that, that you really, you really kill yourself, you know? And so you just have to be professional enough to see that this is politics, it's diplomacy, it's part of the game. People don't mean to insult you. They don't mean to hurt your personally. It's simply part of the professional way of doing this. And, and just, you know, once you're out of the negotiation, you've got to be able to forget this and go home and not worry about it. So but no, I would say the tough phases of your bioimaging. I certainly did not open emails when I had gone home, because I just knew there was going to be something really upsetting coming up and I just wanted to be free of it until the next morning. Yep.

Peter O'Toole (00:37:37):
Okay. So moving off that, into something a bit cheerier, when you do go home, what do you do to relax?

Jan Ellenberg (00:37:42):
So I tend to many days when I get home and I'm not traveling, which now for one and a half years has been the default situation for most of us, I guess. I tend to relax making dinner. So I like cooking. And I like doing stuff with my hands and, and which I certainly don't get to do in the lab anymore because it's, it's just project management and planning and execution. So to do something where you feel useful immediately I, I really love to cook at home. So that's, that's what my wife always says. I just have to give you a sharp Japanese knife and immediately you're smiling when you get home. Even if the day has been really stressful, you're completely exhausted. So because it's this kind of mindless activity, you just know what to do and you do something physical and you see the result pretty quickly. And as my mental mantra is always said, who also loves to cook. The cooking is a lot more fun than lab work because when you cook something, you can almost always eat it. It's relatively rare that you mess it up so badly that you can really not eat it. But in lab work, you do a tiny mistake of the experiment is completely useless right away. So the settling, the cooking is the relaxation for an experiment, a scientist, you can make

Peter O'Toole (00:39:00):
You're cooking. If it goes wrong, generally, you know, quite quickly instead of a week later.

Jan Ellenberg (00:39:07):
So your failure is obvious right away.

Peter O'Toole (00:39:09):
I'm a bit disconcerted that as soon as you get home, your wife gives you a Japanese knife. You know, if you've had a bad day, I'm not sure I'd be wanting to be handed a knife.

Jan Ellenberg (00:39:17):
Yeah, no. So that's a normal days. I go to the kitchen on days where I'm really stressed out and then I go into some exercise courses. So I I've taken up doing a Pilatus exercise, which is a yoga, like thing that you can just do with your body and then the rubber mat. And and I have this routine I do for half an hour. And that, that also, if I had this really needs to be freed up, then, then that's what I do. Cooking is not enough distraction. Then, then that's the first thing. And then after that, I'm the social person again, because some days you're just so overloaded and then you're in this high efficiency problem solving more than if you get into that mode that you go home and you treat the people around you like that, then you're really socially incompatible. It's good to somehow get out of that frame of mind.

Peter O'Toole (00:40:06):
And what's your favorite food to cook? What is your signature dish?

Jan Ellenberg (00:40:10):
Well, I would say I don't have really a signature dish. So I go through phases, mostly inspired by, by really good cookbooks, I would say. So I, last year it was Indian fusion cooking. So I was one of my last trips I did before lockdown in the first pandemic wave was, was to Washington DC. And I ate at a, at an Indian fusion restaurant there, Zika, which is an amazing place. And they, the cook has published a cookbook. So I bought it. And and it's a really good cookbook in terms of the recipes, but also in terms of how they are described, because they really well described. So you can actually do it almost to the restaurant quality if you, if you follow the instructions. So I did a lot of Indian fusion last, last year, and now this Christmas I got a modern Mexican, California infusion cookbook. And so I'm, I'm into that a little bit. Yeah. But so I sort of go through different national cuisines, but then also just a lot of mixtures between Asian and, and Western cuisine, which I think there's a lot of really nice flavor mixtures you can do.

Peter O'Toole (00:41:20):
I don't believe you follow it to the recipe every time you must surely tweak it as you go along.

Jan Ellenberg (00:41:25):
Well, no. So I have a collection of things because often you at home and you don't have the ingredients and then you just make something up. And then if works, sometimes that works spectacularly. Well, sometimes it's, you know, it's all right, but we'll do it again. But the ones I do write them down. So I have a little collection of things that, that, you know, we made up out of the ingredients that were around and that just turned out to work well. And then those, I keep, you know, as a little collection to come back to

Peter O'Toole (00:41:57):
Is there any foods that you do not like

Jan Ellenberg (00:42:00):
Not really, I like to eat essentially everything. I would say this there's just one allergy I have. So I there's one food I cannot eat, which is these very tiny muscles, these Italian heart-shaped muscles. And for some reason I can eat any other kind of muscle, but I cannot eat that one. There must be a weird protein in it that I react to very violently, but that's luckily the only food intolerance I have. So otherwise no worry I take it with the French, anything that moves you can eat. And so then no, I'm, I'm very, you know, vegetable it's I have no problem with fish or meat especially, you know, fresh ingredients and, and good flavors and spices. And then you can always do something really, really nice. And I think preparing your food and also using healthy, fresh ingredients and enjoying eating it to me is a big part of quality of, of private life. I think that's, that's really a very relaxing thing and it happens to be healthy as well.

Peter O'Toole (00:43:02):
Keep it on the food theme, some quick fire questions. What are you going to drink with your food, wine or beer.

Jan Ellenberg (00:43:10):
Wine.

Peter O'Toole (00:43:10):
Red or White

Jan Ellenberg (00:43:11):
Both depending on the food

Peter O'Toole (00:43:14):
Favorite.

Jan Ellenberg (00:43:18):
Between Red or White?

Peter O'Toole (00:43:18):
Yeah, What's your favorite? What's your favorite wine full stop? Do you have a favorite?

Jan Ellenberg (00:43:21):
Yeah. At the moment, a lot of wines from the region here. Or relatively Neustadt an der Weinstraße is an hour away is the Palatinate wine growing region and they have amazing white wines. So they are, I would say, you know, some fantastic Reislings from this, this is the traditional grapes in this area, but then they also have more modern grapes at the moment that they are trying. So things like, Chenin blanc, Weißer or Sauvignon blanc, they have some really, really good white wine. So we have lots of those at home at the moment. And especially for the summer, that's a, that's a favorite. Yeah. And

Peter O'Toole (00:43:59):
Afterwards your Coffee

Jan Ellenberg (00:44:00):
From Germany. So it's more French Italian Spanish, because there's still not enough sun, even with global warming in Germany, too easily

Peter O'Toole (00:44:11):
Tea or coffee.

Jan Ellenberg (00:44:13):
Coffee, For sure. Essentially in the morning. I mean, without an espresso in the morning, almost not functioning,

Peter O'Toole (00:44:21):
That answers the next question, espresso or cappuccino, but you've answered with espresso, I guess at that point, are you an early bird or night owl?

Jan Ellenberg (00:44:30):
Where I would say my most productive time is morning for sure. Not really early. So, so I would say between between eight and one is sort of my core productive time. So anything that is difficult and that requires creativity, I try to do in the morning. So where I, where I need to develop something or, you know, write a paper, write a grant, you know, understand data that's difficult where you really need your brain really to engage and where you get into this tunnel. It's, you know, where you're just thinking about one problem for, for a reasonable amount of time. I have to do that in the morning. I'm not good at that in the afternoon. Afternoons are great for discussion for short things, you know, small tasks. That's not a problem, but, but difficult things morning,

Peter O'Toole (00:45:20):
And you've had dinner, you've had a drink. Are you going to read a book or watch TV or watch a movie?

Jan Ellenberg (00:45:27):
All of these, it depends a bit again on the state of exhaustion. I would say that the, I mean, many nights when you're just exhausted I just watched the news and that's it, and, and go to bed. But then when, when you're really tired and almost too tired to sleep, then a good movie or a good book, both do the job. So it depends on and what

Peter O'Toole (00:45:52):
Type, what genre of film or book,

Jan Ellenberg (00:45:56):
But so in, in books it's really novel. It's mostly so not mystery or a scifi. I'd rather novels so yeah, different writers all over the world. Just, just by written, I like interesting stories and also people that play with language and that have an interesting style of writing. So diverse, I would say in terms of authors movies, lots of things. I mean, so movies mostly at home is for entertainment. So, so they are, I think, you know, not, not too difficult stories, but if I go to the theater to watch a movie in the theater, then, then it's mostly either, you know, our traumas films or things that have a societal or political dimension sometimes. Yeah. So things like that.

Peter O'Toole (00:46:46):
Okay. So moving back into work a bit, you mentioned the advanced imaging center that is just opened up at the EMBL. Can you tell me more about that?

Jan Ellenberg (00:46:57):
Yeah. So that's been the last four years, I guess, of, of work. So when Euro Bioimaging kind of became under control and it was a matter of time until the legal document was published and the infrastructure could start. Then we started something new at EMBL because we realized the core facilities we have are not really set up to serve a huge number of external visitors. We, our core facilities at EMBL they are amazing by now in the nineties, funder founded one of the first big light microscopy facilities in Europe. I think it's still one of the best ones, but the main user basis. EMBL, in Tunnels, it's, it's catering to a EMBL of scientists. They have many visitors, but 70% of what they do is, is to,userve the scientists at EMBL. So if now with Euro Bioimaging and EMBL being still involved in coordinating that lots more people can travel and use facilities. We actually would have a problem with them, but to have enough capacity. And I think the, the other thing is that there is no really technologies that you need to support that are not necessarily yet commercial. You know, many of the new developments in so much more new technology development in the last 10 years than in the decade before that lots of the exciting new stuff isn't commercially available yet, or at least the workflows that you need to get your specimen through them. It's not. And so we've said also the service has to go into a different mode where we have a lot more support and a lot more scientists involved in helping the users so that the research great methods can hit the facilities. And so that's really why we created the imaging center is to, first of all, have a much stronger capacity for our external scientists from EMBL member states, but also be able to have the staff support that, that the latest also academically developed methods can be provided, even if they're not yet commercially available. So that's, that's what the imaging center you said it's just started to do we're in the pilot phase now that the initial projects are coming in from the outside,uin October there will be a completely open call for project. So then we are just like a synchrotron. Anyone can come and do the research here, but at the moment, we are trying to pick projects that are pretty much ready to go for data collection so that we test the service pipelines with projects that are relatively mature. And also with people that already have some familiarity with the type of microscopy they are using, so that there's not such a big steep preparation curve for the projects to succeed yet, but that's that's happening. And so we build this building over the last two years during the pandemic still it's there and it's there on time and actually in budgets, or this was a part of my job. The last two years is to hit the construction board and sit with architects and scientists and construction and engineering firms, and then get this together. But it's no, it's great. I mean, it's really, it's a building made for a visit to us has spacious microscopy rooms to the latest specs. It's not just like microscopy, it's also electron microscopy. So it really goes all the way down to single particle cryo-EM structure, determination and all the way up to organismal, multi photon, and also labor free methods of imaging. And the main emphasis is to integrate these methods together so that people can combine structure and function one project. And so for all of these, it has the latest research. Great. And it's got the infrastructure to keep those instruments working and also the staff that really is there dedicated to help people.

Peter O'Toole (00:50:32):
That was the next question actually, because obviously it's not just the equipment the equipment is great, but the way the technology has moved forward, the expertise needed to support the equipment, not, not to make them run, but to actually apply a user sample on the microscope. That technical expertise is now essential for many of these applications, even though they're easy to use in many cases, actually using it properly is a different problem. And I think I will say EMBL was one of the first places I saw that technical expertise as a potential career for post-docs to go on and not take the classic academic research route, but to become expert in the technology. And actually one of my inspirations was Timo Zimmerman at that point. And I believe Timo being a career technologist an expert now leads part of the advanced imaging center.

Jan Ellenberg (00:51:31):
That's fine. Yeah. So Timo is back after many years in Spain is, is back at EMBL now to help the light microscopy service team. So we have two service teams in the, in the imaging center, one for electron microscopy one for like microscopy and Timo was heading the light microscopy one. Absolutely. Yeah, no that's, I mean, what you said is true, and I think it's embedded this early because it has this service mission. And also here, the service stuff from the very beginning was treated like the research stuff. So there was not a two class system, you know, that you say, ah, you know, you're working in service. You're not real. But, but from the very beginning, it, it was as valuable to be a scientist in service and to be a scientist on the beam line that provides the latest technologies to people as being a scientist who does research because it's it's as essential. And so here that's really a fully accepted career service faculty is on the same level as research faculty. They have the same voice in shaping the agenda and doing strategy. And so there's no no distinction between these two career options. And it really depends on what people are good at and also what they, what they want to do their career. So absolutely that's still like that. And I think the imaging center, because the methods are so demanding, it simply has a higher ratio of service staff to instruments than most facilities that operate only commercial equipment. And so that is why we hope we can support also very advanced workflows. And you're absolutely right. Often the expertise is still limiting either in the specimen preparation or the workflow or the data analysis and that the actual data collection bit, once you've got your specimen, right, is not really limiting the instruments are expensive, but they, they can be used if everything upstream has been done with it.

Peter O'Toole (00:53:22):
I think your staff ratio will also need to be higher compared to a normal university core facility because of the external. Now with internal users, you can train a lot of them. They're long-term investments, they're there for years, so you can train and they will become independent users. The next career technologists can come from that route but I'm guessing the advanced imaging center, most of them will be fleeting moments over the lifetime. People come in fairly transient come in. So they will always be needing a lot of handholding support training going through that. So it's, it will be challenging as it environment for the staff in there whilst exciting, because I guess they'll see a whole variety of different sample types. So yeah, for me, I say Timo was a great inspiration. Seeing that that route is a career path, was was, was brilliant. And it was an eye opener. It was thanks to EMBL and the EMBO course back in 2001 that enabled that who's been your inspiration in your career.

Jan Ellenberg (00:54:26):
Well, I would say I mentioned probably the two most important early mentors already. So that, that was a Jennifer as my PhD advisor, but then also [Inaudible] who taught me a lot of things about, about life imaging. He was a colleague at NIH and then in [Inaudible] where I spent many summers working with him. So I would say early on, they were really the key people to, to inspire me and really in very different ways two role models. I think for research, you know, how do you become really with your whole personality successful scholar and researcher. And they do it in two very different ways, but I think in two completely admirable ways that that one can aspire to, and I'm not at all like them, but I think they were extremely inspiring and, and and, and still are really, both of them are still active. I would say that, that there were many, many fantastic colleagues. And, and especially when I started as a young group leader it was very intimidating being surrounded by so many established people. And you come and start your own group for the first time you think, you know, will never be as good as these people and I'm probably not the real thing. I think this, you know, now you call it imposter syndrome. I think at the time it was just intimidating and you were scared. Yeah. But I think probably the person I learned most from was, was, hain Mattaj was at the, at the time, the head of the unit, I was recruited into it, which was called the gene expression unit. And then later on became director general of the EMBL. Uhnd it's now is heading the, the Human Technopole in Milan. And I think Iain again in a very different way, but he was first, you know, hn amazing scientist, hnd, and many things he did with extreme regard and, and, hechanistic depths, which, which was a new dimension to, to my research. I would say that, that I learned a huge amount from, but then when he became member director general, he had also, he had never done politics and you learn how to do it and very quickly. And so I think also they have problem, the challenges that I was facing in Euro Bioimaging he really supported that a lot. I learned many things from him. So I would say that's probably been the third person. I would say. I feel you learned most from, for my career. Yeah.

Peter O'Toole (00:56:51):
I think just time is ticking over too fast. Have to ask, how did you have within you talked about the politics, within Euro Bioimaging with politicians, but what about the politics between the medical researchers? So your MRI, your pet scan is that community and the microscopists, because we are very different ways of working. How, cause obviously to start Euro Bioimaging is, is about both. It's about imaging. It's not just microscopy. How did you cope? Cause it was pretty rough in the early days. If I recall between these two communities, are they really so different, right?

Jan Ellenberg (00:57:31):
Well. I mean, not really, but, but they, as you say, they have different ways of operating and especially also the systems have very different way of funding the infrastructure. And so that actually was part of the, some of the political problems that the organizations that support more medically oriented research and how it is funded are very different from the ones that support the basic research and then the infrastructure for that. And they, they operate in different ways. And so the project that tried to do both out of necessity early on, initially these were two projects when, when the European infrastructure were perhaps were created it, there were two independent projects, one for biological imaging, one for medical imaging, but then politically in process there was a need to merge them because there were too many and there could only be one for imaging. And we talked about that between the coordinators and we said, okay, you know, we both want to do it. We can do it in competition with each other or we can do it together. And we decided the chances are bigger if we do it together. And I think that was absolutely the right decision at the time, but it did create many downstream challenges. And so some of the political challenges we discussed came from that because different sets of funding organizations that operated with different rules have to be integrated with each other. I think once it comes down to the technology and the scientists, it's actually not difficult. These people like to work with each other and the people who develop instruments, whether it's for animal imaging or for patient imaging or for imaging modern organisms or sets or even protein complexes, they all really love the technology. They really love what can be done with it. What can be seen, what can be visualized and what you can learn. And they love to work with each other. There's absolutely no problem. Yeah. But it's more the level above where people are invested in certain ways of funding research on certain ways of creating infrastructure. And they can loose by that changing and by that becoming more open and more democratic that when you run into problems and I think that's been, you know, a bit more for tradition on the basic science side, that things tend to be democratic. They tend to be open access. They tend to be shared. And it was much less the case on the medical research side because the structures were different. And so there, it was much more apprehension there that, that, you know, they would have to change completely how they operate and they didn't want to do that and all of that. And so that there was a lot of necessity again, to build trust. And I think the, the what has resulted from now, I think to have freely both communities together at many sites, operating joint infrastructure is amazing. That's fantastic. And that's exactly the vision that we started with to build the trust between people that they actually don't take anything away from each other, but that they rather benefit from operating together and from really bringing samples one way or another is, is takes time. It takes time for people to get to know each other for learning to trust each other and, and to see actually it's fun. These are great people as well. And so I think between the scientists, that is not a problem,

Peter O'Toole (01:00:49):
I have realized we are actually up to the hour mark and I, but I've got to ask you before we stop, what do you see as the next big challenge, whether it be technology or biologically, what's the next big thing that has to be developed or solved?

Jan Ellenberg (01:01:06):
I think we've got many in life science. I would say it's, it's still a very young discipline with, with a lot of uncharted territory. And a lot of things we don't understand, I would say there's many challenges for technology. I love microscopy, and I think there's many things we still -cannot see that we need to see. And I think one big area I would like to see happening is that we can understand network dynamics in real time. So I think this is a core of our gap in our knowledge is that we have trouble understanding biological systems because we cannot easily understand how nonlinear large networks work. It's, it's not easy to understand that or from a theoretical point of view, but then also from getting the data that you would need in order to characterize that. And so there, I think our ability to sample that is extremely poor, you know, the many tens of thousands of molecular species you have in a living system that most of them interact with each other and non-linear regulatory loops. We are only scratching the very surface of that information at the moment. And I think technologies to look at that, but also having the theory to actually understand that is not there. Yeah. So I think that for me personally, is an area where I think there's still a lot to do and where we are still only doing, I would call them advanced inventories yeah. With, with all the Omix technologies and the special Omix. And then all of the structure, characterization, all of what we are doing, we are getting a lot better framework information, but to actually say, we've understood how a living system works and we could create it. And we've understood the logic, how it operates. I think that's quite some time in the future because some of the fundamental technology to look at that, but also some of the fundamental theory to grapple with that data and then to get the underlying logic out of it. I think we just don't have it. So I think we need technology. Yes. But we also need more theoretical people to work on living systems because they work in different ways than non-living systems. And there's not enough theorists worrying about that. And what kind of your unit. So I think that to me would be the, the two or challenge.

Peter O'Toole (01:03:32):
I, I cycle back on something earlier. I think one of the biggest challenges with that is the heterogeneity that will be encountered as you go along. And, you know, a cell is a cell. A person is a person and you have a scientist and a politician, and they're very different. This just teasing out the heterogeneity. When you try to understand the one mechanism is going to be, and is a real challenge. One that we will get there. I am in no doubt. I have so many other questions I wanted to ask, but we have run out of time, but thank you so much for joining me today. And thank you everyone for listening, watching to the microscopist. You've heard some great comments about Jennifer Lippincott-Schwartz, which is one of the first one. So go back, listen to that. And there's some other really interesting ones. So please subscribe to the channels, gett Spotify, iTunes, whichever platform you like and hopefully you've enjoyed today. Jan You know, I've learned so much about you today. It's been really eye opening, revealing and, and a real pleasure. So thank you.

Jan Ellenberg (01:04:38):
Thank you very much. Pleasure. I was on my side. It's really been fun and no, it's a great series. And thanks so much for having me

Peter O'Toole (01:04:46):
Pleasure.

Intro/Outro (01:04:49):
Thank you for listening to The Microscopists, a Bitesizebio podcast sponsored by Zeiss microscopy to view all audio and video recordings from this series, please visit bitesizebio.com/themicroscopists.