Stephanie, you are working on cell competition, what is this phenomenon and why is it important?
Cell competition is essentially a Darwinian way of thinking about tissues where they are comprised of cells that are not all equal to one another, so some cells are more fit than others. The more fit, so-called winner cells, compete and kill off the less fit loser cells so that at the end of the day, the tissue is comprised of only the most fit cells. The importance is illustrated by this example from fruit fly wing development, where we find that if we block cell competition, we end up with flies that have unevenly sized wings. Consequently, these flies are a little bit less good at flying then their wild type counterparts, which has serious consequences for their fitness and ability to survive in the wild.
Mechanisms of cell competition were discovered in the 1970s and then scientists seem to have lost interest in it until the early 2000s. Why is that? Why did the field resurge? Did the questions or the technologies change?
I think a little bit of both. On the one hand, the technology progressed quite a bit to enable mosaic genetic analysis of tissues. This first came in the fly and then quite some years later in the mammal and this is really essential to be able to study cell competition within a tissue. In the last 5 to 10 years, I think what has really driven interest in the field forward is the realization that almost all of our tissues are heterogeneous mosaics comprised of clones of varying fitness that compete with each other. This effective mosaicism has consequences for our propensity to develop various diseases and maintain normal tissue function over time. I think we can now use cell competition as a lens to try to understand how these diverse clonal populations within a tissue interact with each other.
Cell fitness and cell competition obviously have many physiological roles. What do you hope the impact of your work is?
If you look at patients suffering from a wide range of diseases, from cancer to many different rare genetic diseases, you can look at the interface between healthy and diseased tissues. And you can imagine that you might have cell competition happening at those interfaces. The idea is that if you can understand how cell competition works, you can develop therapies to promote the growth of the healthy tissue at the expense of the diseased tissue. In this way, I think there's a great potential to use cell competition knowledge to develop potential treatment strategies for a lot of different diseases.
From what I know, there are also possible applications in transplantation medicine.
Yes. There have been some really creative studies looking at this exactly in the context of rejection and whether we can sort of harness cell competition to make engraftment more successful.
Why did you decide to become a researcher?
I think I realized quite late on that I wanted to be a scientist. I wasn't one of these children that are running around in swamps, collecting butterflies. I always loved telling stories, though. Originally, I wanted to study medicine, which got me into a lab and upon joining this genetics lab, I had a very charismatic mentor, who made me realize that telling stories lies at the heart of generating hypotheses and doing a lot of good creative science. Together with the love that I developed for watching tissue morphogenesis unfold, and being in a community with people that were also really excited about this kind of biology, I realized that there is no other career for me.
You have transitioned from Postdoc to group leader, which means that you are recruiting PhD students and other lab members. Now that you see things from a different perspective, what advice would you give your younger self?
I think I would tell myself to really cherish the beginning of projects and to try to savor that time when things are just starting. When I look back at everything I’ve done, that's always the part that's the most fun. It really pushes me to keep going to think about these early brainstorming phases.