Transitions in development – an interview with Jan Żylicz Free

Let's start at the beginning: when did you first become interested in science?

I had a fantastic teacher in high school, where we also had a Biology Olympiad – a national competition around scientific knowledge. What was really nice is that, in addition to some tests, you had to carry out a small research project. The project could be something that you do in your kitchen – something very simple – but you did the experiments, prepared a poster and report. I participated in this biology competition mainly because of the opportunity to do such a research project. It was so much fun and it got me into the scientific mindset for the first time. That's why I decided to study biochemistry and biotechnology during my undergrad.

Following your undergraduate studies, you moved from Poland to the Netherlands to do a Master's degree. What influenced your decision to go abroad and to study at Utrecht University?

I first studied in Kraków, in Poland, which I loved because we were a small class. Students knew all the teachers and university professors, and the course provided a strong theoretical foundation. I thought that if I moved abroad, I'd be able to have more creative input into structuring my education. I was interested in structural biology and applied for a course called Biomolecular Sciences. I had a scholarship, so financially it was also possible for me to go to Utrecht. That move was the most difficult transition I've experienced because it was my first time living abroad alone. I would say that Dutch people tend to be very direct, which is good because it's the most efficient way of communicating, but it took me a long time to get used to that. As I hoped, there was a lot of freedom in the course and it was heavily focused on research. There were two long placements in two different labs and, when I arrived in the Netherlands, I had to immediately choose a lab for the first placement. I looked at who had the last Nature, Cell, Science papers, and I read them to see what excited me the most. I chose a zebrafish lab working on small Piwi-associated RNAs (piRNAs) in the germline. I knew nothing about it at the time but it sounded like cool science, and that's how I got into developmental biology.

In 2010, you then moved to Cambridge for your PhD studies with Azim Surani. What influenced your decision to study in the UK and what did you work on during that time?

I was in a very good position because the lab that I was with in the Netherlands (René Ketting, who's now in Germany) told me that I could stay and do a PhD in his lab. But René told me to also explore other options and then join his team if that's really what I wanted. I thought that was very generous of him and he was proactively mentoring me to apply elsewhere. I ended up applying to just two places: the CRG (Centre for Genomic Regulation) in Barcelona, Spain, and the Wellcome Trust programme in Cambridge, UK. What attracted me to Cambridge was that the programme had rotations, so I could spend a few months in three different labs before choosing the team for my PhD studies. I did a rotation in Azim's lab where, at the time, everything was moving so fast; there were so many amazing people in the team and so much great science. There was always this big question of how DNA gets demethylated and it was a time when everyone was excited about the involvement of hydroxymethylation of cytosine by methylcytosine dioxygenases (Hacket et al., 2013). It felt like a very exciting place to be.

My main project was on G9a (EHMT2), which is an enzyme that puts down a repressive histone methylation mark, H3K9me2. One of the first things that happens epigenetically during germline specification is that the germ cells lose the H3K9me2 mark and we thought it might provide a barrier for germline induction. We did some mouse work and a lot of embryonic stem cell experiments, and it turned out that H3K9me2 is not a barrier; it is important for regulating enhancers and genes in early development, but not per se in specifying the germ line (Zylicz et al., 2015, 2018). So the hypothesis turned out not to be true.

Could you tell me about your postdoctoral studies with Edith Heard, first at the Institut Curie in Paris, France, and then at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany?

I applied to very few places for a postdoc and, initially, it didn't seem like Edith's lab would be my top choice. I wasn't interested in X chromosome inactivation per se, but it's one of the few systems where you can really start asking deep epigenetics questions, because you have the other X allele as a perfect control; you know that regulation is happening on chromatin, and not simply by a transcription factor that can diffuse. But, I remember meeting her at a conference and we had an amazing scientific connection very quickly – it felt infectious. I arrived in Edith's lab at an opportune moment when they had developed a beautiful biological system to study the inactivation of the X chromosome in female mouse stem cells at a really good temporal resolution. We could synchronise the cells and look at the process, hour by hour, of how genes get inactivated on one of the two X chromosomes. My project was to profile these dynamics for the first time – to see all the chromatin changes that are happening and link them to transcription. Together with another PostDoc, Aurélie Bousard, we used this roadmap to determine that loss of histone acetylation is intricately linked with gene silencing (Zylicz et al., 2019). We could show that one of the enzymes, HDAC3, which mediates histone deacetylation, is important for timely silencing. We could also show that, as active marks are lost, specific repressive marks are gained sequentially (Bousard et al., 2019; Zylicz et al., 2019; Tjalsma et al., 2021). The bulk of my postdoc was in Paris – a very fun place to be – and, during my last year, I was travelling between Paris and Heidelberg every week.

What factors are important to you when choosing a lab?

Firstly, good science; clear research questions, cool methods and the feeling that you're discovering something new. Second, it has to click with your future mentor – there has to be this scientific connection. That doesn't mean that you agree on everything all the time; in fact, some disagreement is good, because it creates a more creative environment. However, don't overly focus on the topic of your research. As scientists, once you get deep into any subject, you get fascinated by it.

Is it valuable to move during an academic career?

I moved a lot. In addition to the places I've already talked about, I also spent some time in Singapore. I know many people don't want to move that much, and I understand because it's difficult, especially with a family and one's private life. But I learned a lot every time I moved. People in different institutions really think differently about similar problems, or they find different things interesting, or they ask questions or design experiments differently. You don't realise this until you leave your bubble. Moving just broadens your horizons and the network of people you work with will be much wider, which makes your research more creative and unexpected in some ways.

At what point in your career did you start thinking about independent positions?

I was considering whether I wanted to become a PI during my PhD, but, obviously, I was only seriously thinking about it when I thought I might be eligible or competitive, which was when my first big paper from my postdoc was accepted (Zylicz et al., 2019). Edith told me that I still had a little over a year on my fellowship and that I should spend this time figuring out what I wanted to do and generating preliminary data – and that's what I did. It was so generous of her to let me be in her lab and start working on my next step.

What did you consider when choosing where to apply and accept?

There was a personal situation in that we were two, my husband and I, and we needed to find a place where it would work for both of us. We wanted to stay in Europe but we excluded some countries. Then, I applied to everything because there weren't that many calls at that time, and once we had some options, we would figure out what was feasible. The things that influenced my final choice were the funding situation and how rapidly I could build my lab there, as well as the community and whether there were people with whom I could collaborate. That's what attracted me to Copenhagen.

Describe your first day as a group leader

My first day was 15 March 2020, so I was not even allowed to enter the country! Denmark was one of the first countries to lockdown in response to the COVID-19 pandemic and, therefore, our institute was closed. It felt very confusing. The unexpected things that cannot be prepared for are the toughest. It created a lot of insecurity about whether I even had a job. I managed to move to Copenhagen in May 2020, and it felt weird because everything was empty. It was a big challenge and not the easiest start.

On the flip side of that, what have been some of the best moments?

When one of my PhD students was doing a control experiment and the results turned out to be so much better than anything we were expecting, so much so that we ended up making a whole paper about it (Van Nerum et al., 2025). You can create hypotheses, but sometimes science just offers you observations and, although it takes time to understand the phenotypes, these times are the most exciting.

Was there any aspect of being a group leader for which you felt unprepared?

You become a group leader, primarily, because you published well and, secondarily, because you wrote an exciting project. Maybe a third reason is how likeable you are – do people want to work with you? But your management skills aren't assessed because, at that stage, none of us have that experience. Managing people and large projects has been challenging, but I've been trying to be proactive and get some training. I did the EMBO Lab Leadership course, and one of the grants that I got here in Denmark came with group and individual coaching. One of the best things is that, here at the University of Copenhagen, we have the ‘UCPH Forward’ programme: each year, they select around 24 group leaders from across the whole university, from different faculties and departments, to meet once a month, network and work on some key skills. Having this kind of local community of people at similar stages of their careers has been great.

What's your approach to hiring new team members?

When I started my lab, I had to recruit everyone online, but I learned that you have to use your team during the recruitment – you shouldn't be the only person talking to candidates. It's also important for candidates to see whether you have a healthy lab environment and whether your team is happy, and if so, it makes it easier to recruit the best people. You also need to set some criteria – I want somebody who's a team player but who's also creative and has an internal drive to just go into the lab and start doing experiments. I'm always happy when there's somebody in my lab who starts doing experiments that I never even discussed with them, just because they had an idea. It's good to try and find this attitude.

Could you summarise the research themes of your group?

My lab is divided into three themes. The first one is really epigenetics and development – how gene repression works in stem cells and during development, focusing on autosomal gene regulation, lineage specification, etc. The second theme, which is the bulk of my lab now, is about uncovering how metabolism is talking to epigenetics. Many metabolic enzymes are in the nucleus during early development and we don't understand why. We know that changing the metabolic environment of an embryo or a cell will impact its epigenetic status, which we showed in the first paper from our lab (Van Nerum et al., 2025), but we don't have a deep molecular understanding of how this is happening, because metabolism does so many things. Most of the lab is trying to isolate the most important and crucial regulatory mechanisms of metabolites. The third theme is around translation. We realised that we can modulate metabolism easily with environmental changes, which translates to chromatin. We are collaborating with an in vitro fertilisation (IVF) clinic to ask whether some of the things that we've learned can be applied to IVF treatments; for example, by adding metabolites into media that might help improve human early development. There's something powerful about the idea that, once you've made a fundamental discovery, you investigate whether it can translate into something clinically relevant. We were lucky to find a clinical collaborator fascinated by research, and you need that support because there's a lot of work around ethics, it's high risk and clinical research is a whole different beast.

How did you find your own research niche?

You want to find an approach that is unique and that you're uniquely skilled in but, on the other hand, it's not great to find a niche that no one's interested in. I knew I didn't want to continue with X chromosome inactivation; it's a fairly mature field and there are a lot of people working in it. I was always interested in epigenetics, but the papers that excited me most were about the link between epigenetics and metabolism. It's a good sign when you read a paper and have 10 or 15 ideas for experiments!

Yes, what are the most exciting developments in the field?

I'm most excited about the tools. Mass spectrometry is much better and we can study metabolism during development as we have done in our most recent preprint (Kafkia et al., 2025 preprint). Now, we can use similar tools developed by the epigenetics field to address the same type of questions, but in metabolism, which is a little bit more complicated than epigenetic regulation. The field is moving to studying cause and consequence, and uncoupling different functions of metabolism. Specificity remains a big question; how can a global change of metabolism lead to a very specific outcome?

How important is mentorship in an academic career?

As a junior PI, it's important to have a senior internal mentor who can help you navigate the intricacies of your own institution, and the day-to-day challenges of running a lab – I have Josh Brickman. It's also important to have an external mentor who doesn't have institutional interests, which, for me, has been Edith. Similarly, when you're the boss, it's great to mentor and supervise, but your team might need somebody external to give them career advice. We have a mentorship scheme here where I mentor a different person from the university each year, but not someone from my lab or department. It's very rewarding.

Do you have any advice for someone looking to start a group leader position?

First, be open and know yourself – that's the bottom line for everything that you do in your life. Understand what is motivating you and why you want to do it. Then, apply broadly and only accept places where you can do the science that you want to do. Some people take positions that don't give a lot of opportunities, and that's a very tough experience.

Was there a point when you considered an alternative career?

As I mentioned, I started my PhD with a hypothesis that turned out to be wrong. For a long time, I felt that I wasn't getting anywhere, which wasn't easy. I thought that maybe I shouldn't continue in academia. But, fortunately, everything kind of fell into place in the last year. Still, in Cambridge, there were a lot of companies recruiting and many people were becoming management consultants. I went to quite a few recruitment events and I realised that it didn't seem very exciting. Having that freedom of finding a research question and being able to go to the lab and test it was really motivating. Plus, I would say, I had a very good advisor and mentor, Jenny Nichols, who motivated me to try a postdoc.

Finally, what do you like to do outside of the lab?

We live in Denmark, which is a beautiful country, but with not the best weather, especially in winter. I like travelling and I love diving, so we always try to go somewhere where there's a bit of sun and we can scuba dive. Otherwise, Denmark is a perfect place for cycling. I also enjoy cooking good food, especially French food.

Jan Żylicz was interviewed by Alex Eve, Executive Editor of Development. This piece has been edited and condensed with approval from the interviewee.