Survival of the fittest cells
Not all our cells are equally fit, and only the fittest ones are going to form the tissue. The 'losers' are killed, eaten or pushed out by the stronger cells, explains Stephanie Ellis, cell expert and recently appointed assistant professor at the University of Vienna. The young Canadian joined the Max Perutz Labs in February 2022 to investigate cell competition in skin tissues with immunofluorescence and live imaging. Her ultimate goal is to uncover the basic principles of growth control, which can be the basis for new cancer therapies.
Rudolphina: The research topic you are drawn to is cell competition. What is that?
Stephanie Ellis: Cell competition is essentially a Darwinian way of thinking about cells as if they were communities, like animals in an ecological setting that compete with each other for resources. The fittest and healthiest cells are the ones that form the functional tissue or organ. Scientists initially thought that competition is only happening while tissue is forming. But it turns out that a lot of our tissues are maintained by populations of stem cells that keep building and rebuilding the tissue during our entire life.
Rudolphina: Kill or be killed: What is happening to our less fit cells?
Ellis: For example, when our skin – that is the tissue that I work on – is first forming in embryos, it starts with just a single layer of cells. There we see evidence that the stronger cells are eating the weaker cells in a process known as phagocytosis. Interestingly, once the skin is beginning to form its multiple layered structure, we no longer see this sort of eating behaviour anymore. Instead, the less fit cells are pushed into the upper layers of the skin. Rather than going through the trouble of killing and dealing with the corpse, our cells take advantage of something that the tissue already does: eliminating the 'loser cells' by pushing them out. (laughing)
Rudolphina: What fascinates you about cell competition?
Ellis: Fundamentally, I have always been interested in understanding the molecular principles of how cells talk to each other and how they work together to build complex tissue structures. The idea of cell competition is only one aspect of that. By investigating cell competition, we are trying to figure out how cells can sense the health of their neighbours and decide who is involved in the tissue building process. The work of my group at the Max Perutz Labs is following up on that question.
The Max Perutz Labs were established in 2005 as a joint venture between the University of Vienna and the Medical University of Vienna. Today, around 450 researchers from 40 nations investigate fundamental questions in the field of molecular and cellular biology at the Max Perutz Labs. The Max Perutz Labs are part of the Vienna Biocenter, one of Europe’s hotspots for life sciences. The newest addition is the University of Vienna Biology Building, which was opened this year.
Rudolphina: In which way is your research topic important, e.g. for the development of new therapies and drugs?
Ellis: We are realising more and more that not every cell in the tissue is the same. For example, we expose our skin to sun all the time. The UV radiation can cause mutations in a subset of cells that can sometimes lead to cancer. We try to develop therapies that allow the healthy cells to take over and survive, and the cells potentially carrying cancer-causing mutations to be eliminated. But it has turned out that our skin is actually already pretty good at this on its own. A number of recent human genetic studies have shown that even in skin that appears to be healthy, there are tons of cells with mutations that we would have thought should give rise to cancer – but the tissue looks totally normal. Our tissues are minimising the impact of these mutations and keep them from growing. Cell competition could be the key – but we do not know yet.
We try to develop therapies that allow the healthy cells to take over and survive, and the cells potentially carrying cancer-causing mutations to be eliminated.Stephanie Ellis
Rudolphina: Not knowing and being wrong is part of the normal everyday experience of being a scientist. How do you deal with setbacks?
Ellis: Yes, learning to deal with setbacks is key when you embrace science as a career. But with failure comes something you can learn from. A good piece of advice my graduate school mentor gave me: Try not to design experiments that either work or do not work, but experiments in which the "going awry" is meaningful and tells you something new. For me, the key to getting through science is to have colleagues and other people around that you can commiserate with. Especially in the era of Twitter, when researchers are constantly posting about their great victories, reality versus expectation is getting blown out of proportion. It is important and reassuring to stay in touch with other people that are going through everyday failure and simply talk about it.
Rudolphina: You were a member of the Rockefeller University in New York before joining the cell research team at the University of Vienna. Why did you choose the Max Perutz Labs to conduct your project?
Ellis: I had heard about the international and active research community in Vienna for my entire academic career and I was very attracted by the scientific spirit of the Max Perutz Labs. The institute is extremely strong in biochemistry and molecular biology – that was the asset of Max Perutz himself. I am bringing more expertise on the cell and tissue level and I am going to strengthen that way of thinking. I am excited to collaborate with the great teams here and to get a different perspective – on science and the world.