ABSTRACT

Romain Levayer did his bachelor's and master's degrees at École Normale Supérieure in Paris, France. In between these degrees, he did an internship in the lab of Geraldine Seydoux, at Johns Hopkins University in Baltimore, MD, USA. He then moved to Marseille, France, to join the laboratory of Thomas Lecuit at the Institut de Biologie du Développement de Marseille (IBDM) for his PhD. There, he studied epithelial morphogenesis during the early development of the Drosophila embryo. Postdoctoral work followed in the lab of Eduardo Moreno at the Institute of Cell Biology (IZB) at the University of Bern, Switzerland, where Romain investigated the mechanisms of epithelial cell competition. At the end of 2016, Romain returned to Paris to establish his research group at Institut Pasteur. His lab is trying to understand how the plasticity of behaviour of epithelial cells and the regulation of cell death modulate tissue morphogenesis and homeostasis. Romain was awarded an ERC Starting Grant in 2017 and the SBCF Young Scientist Award in 2018, and he was one of the laureates of La Fondation Schlumberger pour l'Education et la Recherche (FSER) in 2019.

Romain Levayer

What inspired you to become a scientist?

One thing for sure is that I didn't picture myself as a scientist very early on. It's something that came pretty late. I have always been driven by curiosity. But that's one of my problems – I am curious about too many things. For instance, when I was little, I wanted to be an archaeologist. I was fascinated by history and, more specifically, antiquity. But I also liked maths very much. I pictured myself as a maths teacher when I realised there was very little future in archaeology. Science only became a serious thing for me after high school. At the time, I wanted to work at the forestry agency. One option was to go to a prep school in France that combined various science disciplines, including chemistry, physics and maths. There I realised how little we still know about several aspects of biology, and that's the moment I knew I could be really interested by research.

What questions are your lab currently trying to answer?

There are several questions that we are trying to address related to cell death in an epithelial context, but the big picture is the fine-tuning of cell death during development and homeostasis. If you take any tissue, what regulates precisely the rate of cell death? What regulates the distribution of cell elimination in time and space? And how plastic is this process? We can address these questions during homeostatic processes and morphogenesis. We are also interested to know how the tissues cope with local perturbations and how this affects apoptosis. For instance, we can generate clones with different growth rates and different mechanical properties to study how this will influence the survival of the neighbouring cells. Recently, we also started to be interested by how cells commit to cell death and apoptosis. What are the inputs modulating the sensitivity to caspases and at what point does this process become irreversible? That is something that is still not clear in the field of apoptosis, because there are several aspects of caspases that are not related to cell death. Overall, we are trying to develop a global understanding of the plasticity and fine tuning of cell death, combining different scales, from tissue-scale regulation to single-cell analyses, both in physiological conditions and during cell competition.

Your research includes the quantification of several cellular parameters. Does this approach come from your early interest in mathematics?

Yes – I'm always interested in the numbers. What I find absolutely fascinating about biological systems is how complexity is sometimes based on rather simple rules – it's this concept of emergence that comes from physics. Although I always take into consideration the mechanics of morphogenesis, due to the bias from my PhD, I also try to understand how local communication between cells can generate more complex behaviours at the tissue level. I think that these two sides – the biomechanical aspect and the concept of emergence – can help explain local cell behaviours and local interactions that can give rise to more complex features at the tissue level, and these two aspects can only be approached through a quantitative understanding of biological systems.

What would you think has been the most influential publication in your field of research?

I will frame my answer regarding the field of cell competition. A 2013 study from Miguel Torres' lab in Spain showed for the first time that there is spontaneous competition in the early mouse embryo (Clavería et al., 2013, doi:10.1038/nature12389). The genetic approach in this work was amazing. And it was quite quantitative, actually. To me, that was the first illustration that the cell competition process is physiologically relevant and can occur spontaneously during development. There is another paper that very much influenced the way we were thinking about cell competition, but I don't think gets all the credit it deserves. This was published in 2016 by the group of Anne Classen (Bielmeier et al., 2016, doi:10.1016/j.cub.2015.12.063). They characterised the genetic background involved in the specification of cells in the Drosophila wing disc and noticed that changes to this background always give rise to cell elimination or cell exclusion. This actually resulted from a change of the mechanical properties at the boundary between the mutated and mis-specified cells and the rest of the tissue. There seems to be a general process that recognises a mis-specified cell. As a result, you can pretty much explain all the complex features that you see in the wing just by changing the mechanics at the interface of cells and applying simple rules to their behaviour. This article describes a simple mechanism that could be universal and could explain cell elimination in many situations.

What challenges did you face when you started your own lab?

I think the main challenge, which I wasn't expecting, was the loneliness. When you start, no one prepares you to be that alone. There is no one to pat your shoulder and say, ‘yeah, you're doing the right thing’. You have to make decisions all on your own. So this was quite tough. Another thing I found a bit difficult is talking about my doubts and weaknesses. This is despite being in a quite supportive environment with many young PIs around and everyone trying to help each other. And you do have a lot of doubts when you start. The worst part was the year before I started the lab. I had this big wave of ‘imposter syndrome’. Maybe it is easier to talk about your doubts and weaknesses with your lab mates when you're a PhD student or a postdoc, but I found it more difficult when transitioning to a PI position. I do think people are trying to implement things to help with this. For instance, there is a mentoring system [in Institut Pasteur] where you're supposed to talk regularly with more senior PIs. Thankfully, it gets much better once you start to have a critical mass in the lab and can discuss things together.

Romain Levayer trying to work from home during lockdown.

Romain Levayer trying to work from home during lockdown.

Almost three years have passed since you started your lab. What new challenges are you facing now that the imposter syndrome has gone?

I don't think it's ever gone [laughs]. But it's less present. I think it's healthy to have a little bit of it, as well. In a way, I think that the challenges are not so different from what you have when you're a postdoc – you're still trying to find the right question and the right way to address it. One difficult thing is attracting and hiring people, but I was lucky and got very good people from the start; but this is not going to be forever. Shortly, we will have turnover in the lab. Maybe I'm too sentimental about the first generation of the lab [laughs]. I am a bit stressed by that, because everyone will go pretty much at the same time. And then you have to almost start from scratch again. When recruiting, you need to find someone who fits well within your lab, with the way the group is working. But once you realise you have made the right choice, it's probably one of the most satisfying and exciting feelings.

“… two of the things that I value the most are being driven by curiosity and having an open mind.”

What characteristics do you look for when you're recruiting new group members?

I need people who are not afraid of doing a bit of coding, and so I'm looking for profiles that are not so common: people who are doing biology, but at the same time can understand quantitative aspects. But two of the things that I value the most are being driven by curiosity and having an open mind. I'm quite okay with people having their lives and not doing crazy hours, as long as they are intellectually involved. And you can see this when you interview people, from the way they interact with the people in the lab and what kind of questions they ask.

Are you still doing experiments yourself?

Yes, quite a lot, actually. Of course, it oscillates. But luckily, we have all the funding we need for the moment, which means I have time to do experiments. I still like it very much. For instance, every time there is a new tool or hypothesis to test or something to explore a little bit, and no one in the lab has time to do it, I jump at the opportunity. And there is space in the lab to do it, so I'm not preventing other people from doing experiments. Maybe I'm still having trouble making my transition from postdoc to PI [laughs].

What was the best science-related advice you've ever received?

There are many, and yet all of them are a bit mixed up. The main one is to always be very open about sharing things; it could be reagents, results or even unpublished data. Don't be afraid of ‘scooping’. In the end, everyone benefits from sharing, and if everyone does it, it creates a more open community. Maybe I like to believe in karma and paying it forward, but I have the impression that if you're helping others somehow, at some point people will be more prone to help you. Sometimes the general attitude of a field can rely on the behaviours of only a few people. So just having this kind of open mindedness is very good advice.

What would be the most important advice you would give to someone starting their lab?

It comes back to hiring and the identity of your lab. On one hand, you're pressured to hire people quickly and to expand your group rapidly. On the other hand, you should take your time, because you don't want to take on anyone who you are doubtful about. It's really important to take the time to do it right. Even if it delays the hiring a bit, it's better to be sure that it's a good match before rushing to get someone. Another important piece of advice is to never hesitate to reach out and seek advice from colleagues. I tend to be a bit shy and try not to bother people, and you have so much to do when you start that you can very easily lock yourself in your office. But you should not do this, especially if you have other young PIs around; everyone will be happy to share their own experiences. And that's probably the most helpful part.

You're quite active on Twitter: where do you see the value in social media for science and scientists?

I was not always on social media – I don't even have an account on Facebook. But now I have no regrets about trying Twitter. You get to know about a lot of papers that you might not see otherwise, especially in this time of preprints. You also get to learn about different seminars, and especially now [in the context of the SARS-CoV-2 pandemic], it's even more critical to be on Twitter. I would have missed a lot of things if I did not use social media. I don't use it so much as a tool for debating, because I think the format does not allow for proper discussions. I think it gets very caricature-like, very rapidly. But as a way to provide and share information, I find it very useful.

What are your thoughts on the ‘preprint advent’ that we're now facing?

I'm just loving it. To be honest, I actually read mostly preprints. Sometimes it is a bit confusing, because I don't remember if I've read the preprint version or the last version of the paper [laughs]. Between the time you read the preprint and then the actual publication, you really get to know what's going on. It's true that the volume of publications has been increasing. But this was true even before bioRxiv. So, in the end, most of the valuable papers that are preprints will get published at some point in regular journals. I also still think that there is value in the peer-reviewing system. People support the commenting of preprints, but if you want to properly review a paper, it takes time. I think the two systems are very complementary in a way. Referring to your previous question, another motivation to use social media is to use it as a publicity tool to promote your own preprint. So I think social media and preprints are a nice pair.

Do you think taking time to participate in science outreach activities should be more of a priority for scientists?

There is a duality to this issue. Once or twice a year, I participate in this national action in France [Declics programme by FSER], where we go to high schools, present our work to high school students and engage with them. Every time I do it, it's enjoyable and refreshing. And in the end, it doesn't take much time to prepare. So I think it is important for the community. And pragmatically speaking, we should do more science outreach, especially in France. If you want to be efficient with science outreach, you have to reach people who will not spontaneously relate to science. But at the same time, I can see that when you're in the stream of your everyday life, with all the things you have to organise, it can be very hard to find the time, unless there is something already organised with a support system. It would be very time consuming to organise something like that from scratch. And what scientists don't have is time. So if there is a backbone already set up that scientists can enrol and participate in, they will do it, because everyone loves talking about what they are doing.

How did you and your lab cope with the lockdown due to the SARS-CoV-2 pandemic?

We were a bit prepared by the institution. We were not sent home from one day to the next, but we had to completely shut down the lab. There was a minimal number of people allowed on the campus to come in once in a while to take care of the fly stocks, but that was the extent of it. What was a bit difficult to organise was the reopening, because it was very gradual. We had to declare a few weeks in advance who was going to the lab and on which days, which was very challenging for experiment planning. So we tried to make it very collegial, where everyone would have a file describing all the crosses and experiments, and everyone would do a bit of something for the others. I think it worked pretty nicely. And we may have to reapply this, because I'm afraid we have reached a situation where we may have progressive distancing from the lab again. It was really tough for people that have young kids. Despite the fact that the lockdown was over, it took a while before schools and childcare reopened. It was like life was going again, business as usual, but actually it was not. In Paris, you have really small flats, and it was tough for young children to always be at home. I think everyone had different experiences during this time, but I grew tired of all the tweets saying, ‘This is the best time ever to think about science and have big ideas.’ I had maybe five minutes after 1 a.m. to think about myself. In the end, the most important thing was to keep the connection with people from the lab.

“It's very important to have something that makes you step back and consider what really matters.”

What are your views on the feasibility of being both a good parent and a good scientist?

I spend a lot of time with my kids. I'm the one in charge of picking them up, so it means that between 5:40 and 8:30 p.m., it's the ‘no email answering’ period. It takes up a big part of my personal life, but I think attitudes are changing gradually. And you can still cope pretty well with the lab and do things, even with these constraints. The difficult part for me is the conferences. At this stage, I should probably be attending more conferences than I do, but at least family-wise, it is a bit tricky. My wife is not in science, but she has quite a demanding job as well, so every time I go to a conference, it's quite complicated. So I have to limit my participation to make it reasonable. It's a compromise. But at the same time, it keeps you healthy. It's very important to have something that makes you step back and consider what really matters. Parenthood is exhausting, let's be honest. But it also forces you to be quite efficient during the day. Also, we discuss gender equality in science more and more. I believe that part of the solution is to have systematic parental leave for fathers as well. Some postdoc grants, for instance, actually provide the same time for fathers and mothers. I took a three-month parental leave when I was doing my postdoc. Currently, the mental burden is quite often not the same for the father and the mother, but having the opportunity to spend equal amounts of time with the child might help to equalize it.

Could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

Actually, I've been singing in choirs for many years now. I'm still managing to do it. Well, because of COVID-19, not so much now. It's not the most COVID-friendly activity. I will not pretend I'm a super good singer, but I played classical music when I was younger, and the choir is a way to keep in contact with that style of music. I also get a bit of transcendence out of it, I would say. Sometimes, I'm on the verge of saying, ‘Oh, I should stop. I don't have time anymore’, but it keeps me mentally healthy and happy, so I keep going.

Romain Levayer's contact details: Institut Pasteur, Department of Developmental and Stem Cell Biology, CNRS UMR 3738, 25–28 Rue du Dr Roux, 75015 Paris, France.

e-mail: romain.levayer@pasteur.fr

Romain Levayer was interviewed by Inês Cristo, Features & Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.