Verena Ruprecht received her PhD in Biophysics from the Johannes Kepler University in 2010 for her work on developing single-molecule super-resolution imaging tools in the lab of Gerhard Schütz. Following a research visit in Didier Marguet's lab at the Centre d'Immunologie de Marseille-Luminy (CIML) in France, she moved to the Institute of Science and Technology (IST) in Austria for a postdoc, working jointly with Carl-Philipp Heisenberg and Michael Sixt. There, she discovered a unique amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Verena started her independent laboratory at the Centre for Genomic Regulation (CRG) in Barcelona, Spain, in September 2016. Her group combines genetic and biophysical methods with multi-scale imaging and mathematical modelling to study cellular dynamics in embryo development. In 2020, Verena was selected as an EMBO Young Investigator and in the same year awarded an HFSP Young Investigator Grant for a collaborative project to study the biophysics of zebrafish fertilization.
What inspired you to become a scientist?
I'm simply a very curious person, and so I was naturally drawn to science; in school, I read many books and was interested in everything about how the world works around me. By then, I already had a passion for mathematics and physics, and was fascinated by how we can come up with concepts that help us grasp complex things in the world – and that we can find rules in this complexity. So, the reason I decided to study physics was that, to me, it's the basis for all natural sciences. I did always have it in the back of my mind though to later work on a life-science question, and the university I studied at was one of the first in Austria to have a programme including an interdisciplinary study branch of biophysics. When I saw that, I knew right away that would be something for me.
And advancing imaging tools was your entry into biophysics research?
Indeed. My PhD professor was pioneering the field of single-molecule microscopy, and at that time we were building our own custom-made microscopes to visualize the dynamics of proteins and lipids inside the cell. Everything is stochastic at that scale, but the molecules still come together to carry out specific functions and make a living cell as the basic building block of more complex multicellular structures, which still fascinates me to this day. Now in my lab, we are using imaging-based technologies to visualize biological processes across multiple scales – from molecules to cells, up to tissues. We use zebrafish embryos, which are a beautiful system for in vivo live imaging approaches.
What questions are your lab working on at the moment?
What we are very interested in is how the embryo takes shape and builds a functional tissue organization. We are trying to tackle this question from the single-cell level, and understand not only how cells generate forces, but also how they respond to them, as well as the different force-feedback mechanisms that are required for cells to adapt their shape and function. In this respect, the actomyosin cytoskeleton is of course very interesting because it's one of the main mediators of cell shape changes at the single-cell level. It's also fascinating to study the cytoskeleton in terms of bridging scales – from the molecular process of filament assembly up to the cellular scale, and the emergence of collective phenomena and tissue architecture. How mechanical and physical processes further integrate with cell signalling and function are exciting questions for us to study. We also ask fundamental questions, such as how an embryo can cope when things go wrong. Often, in developmental biology, the embryo is only studied in its normal state, but what actually happens if we perturb the system? How robust is the developmental process and what cellular mechanisms are in place that allow the formation of an organism despite errors in development?
The stories you've recently published are quite diverse, from cellular mechanosensing and mechanotransduction to phagocytosis and innate immunity in early embryogenesis. How do you identify the interesting questions to work on?
I think in biology we still face enough fundamental questions, and we should dare to tackle them – so in our lab we also do explorative research using imaging, and here it's important to always have a hypothesis in the back of your mind. One of the things that has been key for us is not discarding the ‘bad’ embryos, but looking into things that are not normal. For example, our recent phagocytosis paper emerged from doing stress perturbations in the embryo, where we wanted to change the mechanical properties of cells and see how development can still work out fine. But the important observation came from embryos that apparently didn't look good and had a lot of fragments in the epithelium. We could have easily trashed this observation, but we followed it up because we thought that maybe there was something to it, and after many further experiments, we identified an epithelial clearance mechanism for apoptotic cells. Another approach we follow is to establish bottom-up experiments by taking cells out of the embryo and studying how we can control single-cell and collective behaviour in synthetic assays that mimic different environmental and tissue conditions.
“I think in biology we still face enough fundamental questions, and we should dare to tackle them […]”
What's your approach to collaborations?
I have always worked in interdisciplinary teams, from the beginning of my PhD, and seeing how people who come from different disciplines think – so the intellectual exchange – is very important. Collaborations also come naturally because in biology you are using different technologies; however, the ultimate aim is not just to use these technologies and generate data, but the question really is what do you make out of that data; how can you come up with more generic descriptions from the data that tell you something fundamental about biology? That's why we also use mathematics and physics to conceptualize the findings, and we collaborate with theory people to build models.
You have now been a group leader for nearly 5 years. Looking back, can you talk about the challenges of starting a lab?
I think starting a lab is like establishing a startup company. It's very intense work and you really commit your life almost fully to that in the first years. Apart from recruiting people and getting funding – and here I am very grateful for my institute's core funding that enabled the work we our doing – leading a lab is also very different from being a postdoc, because you have to balance multiple projects. I also have a daughter, who was just a one year old when we moved to Spain, so it was also important for me to balance work with family.
And what advice you would give to someone who is about to start their lab, including scientists with families?
I think it's difficult to give general advice, but the most important thing is to enjoy what you do. I'd also say that it's important to connect with your peers and be able to reach out for help. Sometimes, we can feel that certain issues are only happening to us, but actually, it turns out that most people struggle with them in one way or another. We had a mentoring group, which was something I had to get used to because I often think I can solve conflicts myself. But opening up and sharing your experiences really helps and allows you to connect to other people. As a parent and scientist, sometimes stepping back and looking at the bigger picture of why you decided to have kids or why you decided to do science will give you back the joy when you are feeling stressed. It's important to realize and appreciate what you are getting back from the situation – not just feeling that you are only giving.
“[…] opening up and sharing your experiences really helps and allows you to connect to other people.”
Finally, could you tell us something about yourself that wouldn't be obvious from your CV?
I love doing sports and being in nature – finding new hiking trails, mountain biking, skiing, or simply enjoying going for a walk with family and friends. It's really important to have some complementary activity to being in the lab and sitting in the office, and it is a great way for me to disconnect. Now that my little one is a bit older, we can do bike tours together, which I really enjoy. Another thing I do with her, which may be typically Austrian, is baking cakes and making really cool sweets. We just like creating things in the kitchen, which is also kind of like doing an experiment.
Verena Ruprecht's contact details: Centre for Genomic Regulation (CRG), C/Dr. Aiguader, 88 PRBB Building, 08003 Barcelona, Spain E-mail: firstname.lastname@example.org
Verena Ruprecht was interviewed by Máté Pálfy, Features & Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.