Transitions in development – an interview with Aleksandra Pękowska

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

I think I've always been interested in science. Although, when I was a kid, I was also fascinated by history, and actually this fascination led me to attend a high school that was preparing us for studying history and law. However, in the end, I decided to apply to two different universities. One application was to the philosophy faculty, and the other was to the faculty of natural sciences. I decided then that natural sciences would be the best option for me.

Why did you decide to focus on biology in the end?

I think it was related to the fact that I never really felt that I was learning biology; it was always just sinking in very naturally.

You completed your PhD at the Centre d'Immunologie de Marseille-Luminy (CIML), France. What were you working on at the time?

I found an opportunity in Marseille to study regulatory elements and their epigenetic signature in development. This was in Dr Pierre Ferrier's lab, where Dr Salvatore Spicuglia was using high-throughput genomics approaches. I had always wanted to know how cells know who they are, so I decided to join the lab. We were studying how cis-regulatory elements are activated during the development of T cells, how we could find these elements in high-throughput ways, and how this activation of enhancers, and regulatory elements in general, is related to cell identity choices.

I understand you then moved to the European Molecular Biology Laboratory (EMBL), Germany, where you worked with Drs Wolfgang Huber, Lars Steinmetz and Paul Bertone. What were you working on, and how was the experience of working across three groups?

It was wonderful. I met Wolfgang when I was doing my PhD in Marseille. Even back then, during my PhD, I understood that computational biology was going to be very important for the projects that I wanted to pursue in the future, so I had already started learning computational techniques. I applied to Wolfgang's lab, having the idea in mind that it would be great to have the dual skills of computational and wet lab biology to study how development is related to chromatin architecture, and how chromatin architecture could contribute to transcriptional regulation and development. I was awarded an EMBL interdisciplinary postdoctoral fellowship called the EIPOD Fellowship, which entailed working with different labs. So, Wolfgang and I approached Lars, who was a geneticist at the European Bioinformatics Institute (EMBL-EBI) specialising in high-throughput approaches. We also approached Paul, also at the EBI, who also had this dual expertise. It was wonderful, because I learned how to approach my research problem from different angles, and how to inject a very statistically principled way of thinking into everyday scientific and wet lab thinking. So, I think this step was very important in my career.

You then moved to the USA for postdoctoral work with Dr Rafael Casellas. How has moving countries influenced your career?

Oh, dramatically, because every institute has their own way of doing things. My very first move was to France, and then I went to Germany. The move to Rafael's lab was very important because, in the USA, I was able to combine my computational and wet lab experience. I went back to the immune system in a way, because we were using B cells, but we were addressing very similar questions (and using very similar assays and computational tools) to the ones I had been working on at the EMBL. So, that was very instructive, because I was able to combine all my experience thus far. But the move to the USA was also important because the environment at the NIH is different – everything is much bigger, and it's very exciting. You see more clinical studies, and more of this combined way of thinking. I think that was very important for me.

You then returned to Poland to establish your own lab at the Nencki Institute of Experimental Biology. How did you form your research niche for your group?

I don't think I was actively working on forming a research niche. I was just totally fascinated by the development of the nervous system. When I was at the EMBL, I started reading about astrocytes, and it struck me that knowledge about the mechanisms that regulate human astrocyte development and functions is scarce. There is beautiful literature on the impact of astrocytes on neurons and on the interactions between astrocytes and neurons, but we lack an understanding of how astrocytes evolve. At the time, evidence was accumulating indicating that astrocytes might evolve even faster than neurons, and that these cells are much more complex in the human lineage than in non-human primates or rodents. This just struck me as a fascinating thing to study. So, I think that reading a lot of literature can cause questions to emerge that allow you to form your niche.

It sounds like your work has become even more interdisciplinary by also incorporating evo-devo questions. How have you found moving into that space?

I really love it, and I think that it's a very nice environment. I've met a lot of fantastic people, and there's so much space in this field because there are so many things that are yet to be discovered. The immune system is complex, but it is largely understood, even though we discover new things constantly. But understanding the evolution of the nervous system is still a pretty broad problem, even though a lot of knowledge has been gathered over recent years. That's why I think that people in this field are so collaborative: they want to push things forward. There are a lot of things that haven't been addressed in the glial field, for instance.

Can you summarise the research themes of your group at the moment?

Broadly speaking, we are interested in chromatin biology and genome biology. So, on the one hand, we continue what I was doing in the past, and we investigate mechanisms that orchestrate three-dimensional chromatin structure and how this structure matures during development. This is a large branch of our research, and we have two big projects focusing on CTCF, which is a chromatin organiser. On the other hand, we are working on human brain evolution, and we are approaching that from the perspective of astrocytes. For a long time, astrocytes have been considered to be a purely homeostatic component of the brain, yet new data indicate that astrocytes are crucial for the formation, activity and pruning of synapses. We focus on the potential contribution of changes in astrocytes to brain evolution; we would like to understand which DNA regulatory elements in astrocytes orchestrate astrocyte evolution, and how this is connected to brain disorders and the acquisition of the unique capacities of the human brain. These two branches of our research have started intermingling more and more as we see interesting links between chromatin architecture and astrocyte evolution.

What were your most important considerations when looking for group leader positions?

I was looking for a relatively stable position because I think that's the most problematic aspect in transitioning to a PI position: you would like to have secure funding for longer periods of time. I also wanted to go back to Poland. I had heard about the Dioscuri Programme, a project that emerged from the Max Planck Society in Germany. The programme is operated together with the Polish National Science Centre and funded mutually by the German and Polish Ministry of Science and Education. This very generous grant funds the establishment of a team in Poland, and there is also the opportunity to renew it once. This ability to finance my research in a more stable way was very important for me.

What has been the most challenging aspect of transitioning to a group leader role?

I think that, as postdocs, we are not really trained in managing a bigger group of people. I did not find it challenging myself, but the number of people that you get to manage very quickly can be daunting. And, of course, there is a lot of administrative work. When you are a postdoc, you're focusing on doing research, which is wonderful, but once you become a PI, you spend long hours addressing administrative matters, which is not as exciting as research.

And, on the flip side, what do you enjoy the most about running a research group?

Talking to people, by far. I love having meetings with my team members to discuss the next steps and the data, thinking about what the data tell us, coming up with additional controls, and challenging our observations to think about what is really going on.

What has been your approach for hiring new team members?

I have at least two meetings with the candidates, and I invite them to visit the lab whenever I can, although sometimes I have candidates from Asia, and it's a bit difficult for them to come in. My general approach is to find people who are brilliant and who want to discover something. I'm not necessarily looking for experts in a particular field, because in Poland the fields that I have been working on are not very developed. For example, I think we are most likely the only lab in Poland that uses induced pluripotent stem cell systems in non-human primates, so I'm not expecting to see people with experience in that field, but if you are willing and smart you can quickly gain enough skills to perform these experiments. That is my approach: to find people who are collaborative and who want to discover stuff together with me.

It sounds like your research themes are quite interdisciplinary and broad, so do your lab members come from different research backgrounds?

Absolutely. We have bioinformaticians in the lab and we have wet lab biologists. We have experts in chromatin, experts in cytoskeleton and experts in more technical aspects. We also have two people who are very inclined towards engineering, so they are implementing new protocols. I think that the strength of our team is that people are not afraid of trying new things, and we have been able to implement a lot of tools in the lab that are cutting edge because people are willing to try, even though they have never used these approaches before.

What advice would you give to people starting their own labs?

I think that it's essential to form a team that is on the same page as you are and that has a drive and passion for science. Finding friends with whom you can discuss your science is also important.

What is your approach to mentorship within your lab, and have you had any significant mentors who have influenced this?

I think all the people I worked with gave me something unique and important, starting from my mentors at university. I had an individual programme of studies, and I was mentored by Professor Grzegorz Bartosz and Dr Łukasz Pułaski from the University of Łódź, who taught me a lot. Then, during my PhD, Salvatore Spicuglia taught me how to manage scientific problems and how to keep on asking questions. My postdoctoral mentors gave me insights into how to mentor other people, but also how to approach scientific problems through discussions. I try to use this discussion-based approach in my own lab. For example, I aim to be in the lab every day when I'm not travelling, and even if I travel my team knows that they can just drop me a line and we can have a Zoom call. Apart from this, I have meetings with each lab member at least once a week, and I really like discussing their everyday progress. That's how I approach mentorship because I think that discussion is essential.

I saw on your lab website that you were involved in the SONAR project during the pandemic. What did that involve, and how did you find the experience of directly contributing to public health approaches?

SONAR came about because we wanted to contribute to the COVID pandemic response. Back then, I think we were three or four people in the lab, and everybody wanted to work and to do something about it. I was lucky because we were approached by a group of mathematicians who wanted to model a pooled testing procedure. Back then, the tests were outrageously expensive, so we decided to implement this pooled testing procedure, which allowed us to test everyone in the Institute who wanted to get tested on a weekly basis for a long period of time. We were also able to test volunteer medical students, which was very important as they would be going to treat patients in the hospital. We were financially supported by the Polish government, and we were able to work in collaboration with other places that were doing this kind of screening routinely. My experience was that introducing this kind of approach to the market is very complicated, and it's extremely important to make sure that sensitive data is being well taken care of. I must say that we were helped by several people here at the Institute who we were lucky to have in our team, so it was a good experience, although I wouldn't like to repeat it and I hope a pandemic won't happen again!

We talked at the beginning about how you considered studying history or law at university. Have you ever considered a non-academic career path, or did you always want to be in academia in some form?

To be honest with you, I never considered any other path. There were temptations, especially in the USA, where companies are very outgoing in their attempts to contact you and it's very easy to get interviews with them. I went for some interviews just to check whether that sort of career could be for me, but I decided that I would like to give an academic job a try.

Finally, what do you enjoy doing outside the lab?

I love hiking, and it's by far the activity that I enjoy the most. I also like stargazing, so I have a telescope, and I enjoy reading books too. So, when the skies are grey and cloudy, then you will find me with a book!

Aleksandra Pękowska was interviewed by Laura Hankins, Reviews Editor at Development. This piece has been edited and condensed with approval from the interviewee.