Jakub Sedzinski is an Associate Professor at the University of Copenhagen and the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Denmark. After his undergraduate and Master's degrees in biotechnology at the University of Wroclaw, Poland, he completed his PhD in Prof. Ewa Paluch's lab at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, where he studied biophysical aspects of fundamental cell behaviours. Next, he moved to the University of Texas at Austin in the USA for a postdoctoral fellowship with Prof. John Wallingford. There, he became interested in how cell-level mechanics influence the complex development and maintenance of tissues like the mucociliary epithelium. In 2017, he started his own lab in Copenhagen where he continues to integrate biophysics with cell biology and developmental models in order to elucidate the relationships between cell and tissue mechanics and cell fate acquisition in epithelial tissue dynamics. We spoke with Jakub over Zoom about his career and how his cross-disciplinary approach to research is driven by his fundamental passion for learning new things.
What inspired you to become a scientist?
I'm afraid there is no beautiful story behind it! In fact, as a child I wanted to design cars. I used to spend a lot of time drawing cars and designing car interiors. But I was always good at school; I love the thought of gaining knowledge and had fun learning subjects like math, physics or history. I was always very energized by grasping new concepts and new ideas, and I think that this naturally evolved into a passion for science. During university, I studied biotechnology. It was a challenging 5 years and involved learning lots of complex subjects, but it allowed me to explore many aspects of biology, from physiology to the intersections of biochemistry and physics, which was a perfect fit for me.
After your undergraduate degree, you spent some time in a molecular plant physiology lab in Potsdam, Germany. What did you learn there that you still apply in your current research?
That was a part of my Master's degree, at the Max Planck Institute of Molecular Plant Physiology. This was the first time I experienced working in a large international research centre with state-of-the-art methodologies and interdisciplinary groups, doing high-level research. In that environment, I was able to try everything I wanted in the lab without many limits. You just had to have a good research question and the willingness to try things. Being at this institute showed me that you can look at scientific questions from different perspectives and multiple angles, which was fun and exciting. That was an extremely motivating experience. I think this is where I gained the inspiration and appreciation for working within multiple fields of science and applying knowledge and methodologies from different fields.
For your doctoral work with Prof. Ewa Paluch at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, you studied biophysical mechanisms of cytokinesis. How did you first become interested in biophysics?
I very much liked plant research, but I was still curious about how other systems worked. In Ewa's lab, I again had the chance to just learn new things and try new approaches, such as the laser ablation system the lab was establishing at the time with Jean-Yves Tinevez, who was then a postdoc. Biophysics is quite different from plant physiology, but the learning curve wasn't so steep because I had great mentors in Ewa and Jean-Yves. It was a lot of fun and ended up being a painless transition.
I started out my PhD looking at oscillations of the actomyosin cortex in mammalian cells. We were trying to construct an anuclear minimal cell to study the biophysical behaviour of these structures. As we started looking into the biophysics of different aspects of cell behaviour, I became interested in cytokinesis and membrane structures called blebs, which occur in dividing cells. For many years, people thought blebs were just an artifact, but it turned out that blebs are actually important and function like a safety valve for releasing pressure in the cortex during cytokinesis. They help maintain the cytokinetic furrow in the centre of the dividing cell and allow for proper division. Personally, witnessing how finely tuned control of cell mechanics impacts essential biological processes was deeply inspiring, and has shaped the course of my entire career journey.
In 2011, you started an EMBO-funded postdoc with Prof. John Wallingford at the University of Texas at Austin, USA. Was this move a big adjustment for you?
Yes, it was a big change. In Ewa's lab, I was looking at pure cellular mechanics. For my postdoc, I wanted to apply this knowledge to embryos. It happened that John was giving an invited talk in Dresden while I was doing my PhD. He's such a great, charming speaker and he showed us some very impressive techniques using Xenopus laevis frog embryos. I remember chatting with him about my PhD research and the questions I was interested in. I saw a huge potential in taking what I had learned about cellular mechanics and applying it to developing embryos, and I think Xenopus was perfect for this because frog embryos are easily accessible. Especially because the skin of the embryo, the mucociliary epithelium, allows you to apply mechanical perturbations very easily. On top of that, we can image cellular behaviour in frog embryos quite easily. So, this was a great system. It took some time to learn to combine mechanics at the cellular and embryo levels, but it eventually worked very well.
The move was also a big adjustment in lifestyle. You know, everything is bigger in Texas! I really enjoyed Texan and American culture; the mindset of people there is so different. It took time to get used to, but now, I miss it. It was actually difficult to return to a European style of living when I moved back! I met so many good friends there and I started doing a lot of outdoor activities. Austin is a beautiful place for music and barbecues, and it always has fantastic weather for hiking. Somehow, despite being born in Poland and now living in Denmark, I very much liked the hot weather in Texas almost all year round.
In 2017, you started your own lab at the University of Copenhagen, Denmark. What was the biggest challenge you faced as a new PI and what advice would you give to researchers who are aiming to start their own labs?
As a postdoc, you are very much responsible for yourself. But once you have your own team, you are responsible for your team members, and I also think that to a larger extent you're dependent on them. One of the biggest challenges for me was understanding how the people in my lab work as a team, and then making sure of generating a stimulating atmosphere for them. If you can do that, the rest will kind of self-organise. Another challenge is to learn to let things go. It's often the case that we think our way is the best way. But as a PI, I learned that there are different ways of doing the same thing, and you sometimes just have to let people do things their way. Trust people, do not micromanage them, believe in their capabilities, and learn what stimulates your team members, because everyone is different, and everyone is an individual. I think it's really important to take your time to understand what motivates people and how to talk to them. I would also suggest that you need to trust your own gut feelings. Of course, you should take feedback and listen to your colleagues, friends and team, but at the end of the day, when it comes to your research, you should trust what you think would work. Really trust in yourself, and trust in your team.
Trust people, do not micromanage them, believe in their capabilities, and learn what stimulates your team members, because everyone is different and everyone is an individual.
What are the main questions your lab is currently trying to answer?
The main theme of the lab is mechanics of the mucociliary epithelium, the epithelium that lines our respiratory tract. Defective homeostasis in this and similar types of tissue is associated with disease such as asthma, chronic obstructive pulmonary disease (COPD) and cancer. To study the development, homeostasis and regeneration of the mucociliary epithelium, we use two model systems: Xenopus embryos and organoids derived from biopsies from individuals with diseases. Using these two systems, we are trying to understand how mechanical forces shape this epithelium while looking at the interplay between tissue morphogenesis and cell fate. How do cells that are undergoing differentiation probe the mechanics of their environment, and how does this mechanical environment affect the behaviour of the cells? For many years, we could only infer forces in vivo, but there has recently been huge progress in directly measuring and probing forces in developing embryos. This allows us to ask even more complicated biophysical questions and understand the development of embryos and tissues like the mucociliary epithelium at a much deeper, more detailed level.
You recently received a European Research Council (ERC) Consolidator Grant to study the interplay between mechanical forces and cell fate during development. What does this award mean to you and the trajectory of your research?
What we proposed with this grant is integrating multiple types of data, including mechanics, to understand tissue development. The current state-of-the-art involves single-cell sequencing, metabolomics, transcriptomics and so on, but in all these approaches, the influence of mechanics is rarely considered. We aim to integrate cell mechanics into the multi-omics world, because cell behaviour and function is ultimately tied to generating and sensing forces. I'm very grateful to the ERC for supporting this fundamental research. Currently, it can be difficult to get funding for projects focused on fundamental questions in biology. But in the end, these projects give rise to translational approaches. For us, this ERC grant means we are on the right path and that our ideas are appreciated in the field. I think that this will hopefully allow us to achieve the dream of seeing our basic research evolve into something more translational.
We aim to integrate cell mechanics into the multi-omics world, because cell behaviour and function is ultimately tied to generating and sensing forces.
Your research takes a cross-disciplinary approach to understanding tissue architecture and development. What do you find most challenging – or rewarding – about interdisciplinary research?
In the lab, we have people from several different fields: engineers, computational scientists, molecular biologists and so on. It's a really great group of people. And it's kind of nice to work in an environment where you are surrounded by people much cleverer than you in different disciplines! I think the most challenging thing in interdisciplinary research is just taking the first steps out of your comfort zone. It's often a steep learning curve to learn the language of another discipline, so you have to be persistent in talking to a lot of people, reading a lot, and trying to understand the new system and its methodologies. This might be challenging, and it takes time, but it definitely pays off. Once you learn the other language, it's so much easier to communicate with specialists in other fields. At the same time, if you want to communicate your own research to someone that doesn't work in your field, then you also have to think about your project simplistically in terms of core concepts, so that the other person can understand the basic idea. Learning to do this makes you think about your own project much more deeply. Altogether, this gives you the ability to approach your question and the biological process you study from another angle. I find the whole process really enjoyable in and of itself.
Are you still doing experiments yourself?
Yes! For the first few years after I started my lab, I was basically working like a postdoc. Over the past 2 years or so, I had been doing much fewer experiments, but recently I'm actually returning to the lab. When new people join the team, I really enjoy helping to train them. It's always fun to go back to your inherent passion for doing experiments. I miss it, and I have found that you get ‘out of shape’ very fast when you're not practising regularly. I used to be able to do hundreds of embryo microinjections in half an hour. Now, first I have to just figure out where equipment and reagents are in the lab!
What is the best science-related advice you ever received?
The best piece of advice I've had was from John Wallingford, and it was simple: “Read and learn how to write.” Learning how to write will save you a lot of time in a scientific or research career. Writing fast, writing well, writing clearly and concisely in a way makes people excited about your research – this is a skill that will definitely make your life easier.
Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?
I'm interested in so many things! I do triathlons. I love driving motorcycles – this is a passion I developed when living in Texas. I recently started to learn how to play the trumpet. I have an 11-year-old dog, so I like walking the dog and having a relaxing time outside. I sometimes still enjoy drawing cars. When I visit my parents, they still have my old sketches stored in boxes. It's cool to see that I predicted a lot of designs that are now being applied to current cars! It's funny, because thinking about design is also part of what I do in the lab. I think about how to build tissues, how they come together and ultimately become an embryo. I'm very intrigued by the idea of applying synthetic biology methods in order to understand the ‘design’ of an embryo.
Jakub Sedzinski's contact details: Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Denmark.
Jakub Sedzinski was interviewed by Amelia Glazier, Features & Reviews Editor for Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.