Maria Sibilia

Maria, I always associated you with Italy, but you actually grew up in Switzerland.

Yes, I was born and raised in Switzerland. My parents are from Southern Italy and I have both citizenships. I would say, genetically I am Italian, but epigenetically I have been strongly influenced by Switzerland.

So, when and how did your interest in the biological sciences develop?

I remember looking at medical encyclopaedias as a child. The human body fascinated me. Ever since I was five years old, I wanted to study medicine. But then, during my last year at school in Chur, our biology teacher taught molecular biology and genetics and I knew, that’s what I wanted to study. At that time, I had already enrolled at the University of Zurich and had even gotten into medicine. But I realized that I wanted to understand the diseases and not just treat them, so I gave up my medical studies - a shock for my parents - and looked around for a biology course. The curriculum in Zurich was very traditional, focussed on organisms, but I wanted to understand the molecular mechanisms of disease.

Back then, I spent a lot of my free time in Italy and started to enquire about possibilities there. The Italian embassy in Bern were very helpful and pointed me to Pavia, where I finally enrolled in biological sciences. I chose the branch of molecular biology and genetics, and in Pavia that was very much focused on human genetics. For my Master's thesis, I joined a lab that was researching brain tumours. And guess what molecule I worked on: my topic was the expression of the EGF-receptor in lymphoblastoma!

That was more than thirty years ago and the EGF-receptor is still a main focus of your
research today! Where did you turn to after you completed your Master’s degree?

Around that time, in the late eighties, the first knock-out mice were created and I was fascinated. If you want to understand cancer, that's the technology! I realized that, for my PhD, I wanted to work in mouse models and use this kind of genetic manipulation. One of the first people to make transgenic mice was the Austrian biochemist Erwin Wagner. He had just won the EMBO Gold Medal and when I came across a review by him, I was totally fascinated. I planned to do my PhD at his lab in Heidelberg, but Erwin had just moved to Vienna to become a Senior Scientist at the newly founded IMP. So instead, I joined a young group leader who was about to establish a knock-out lab in Brescia. The team was workingon muscle differentiation and the plan was to knock out myogenin, a transcription factor that controls muscle differentiation. Things did not go according to plan, though. I guess that in 1989, one of the few scientists who could do knock-out mice successfully was Mario Capecchi. I tried for two years, but I never even got any targeting in ES cells. In the end, I did my PhD on a hemorrhagic virus that infects rabbits.

You did end up in the Wagner lab eventually.

I still wanted to work with Erwin Wagner and decided that, since he was in Vienna, I would go there for my postdoc studies. It turned out they had run into similar problems with the knock-out mice. When I interviewed for a postdoc position, they had just succeeded for the first time to target the Fos-allele and were about to target Jun. The trick the scientific community had learned in the meantime was to use isogenic DNA.

You joined the Wagner lab in December 1992 and stayed until 1998.

Yes, I was a postdoc for three years and then spent two more years as a staff scientist. When I came to the IMP, most people in the lab were working on AP-1, on Jun and Fos. However, there was one PhD-student who worked on the EGF-receptor, struggling to overexpress EGFR in ES-cells. Erwin remembered that I had some experience with that molecule and suggested to continue in this direction. My plan was to knock out the EGF- receptor in mice. And what can I say, as soon as I joined the IMP, everything miraculously worked out. It felt like a blessing from heaven!

We succeeded in generating mice lacking EGFR and published our results in Science in 1995. The phenotype of these knock-out mice was very complex and influenced by the genetic background. We saw effects in the brain, placenta, skin.... so I started working on various different organs. The great thing was, in Erwin’s group you were allowed to do anything. He gave us complete freedom. When I presented my plans, he encouraged me to go ahead.

For my brain studies, I was able to collaborate with Adriano Aguzzi, but there was no-one in our group who had experience with skin. Erwin was quick to point out that he knew Fiona Watt at the Imperial Cancer Research Fund. He promptly called her and two weeks later, two postdocs arrived from London to isolate keratinocytes with me.

When you look back at your time at the IMP, what stands out in your memory?

The time at the IMP was really special, everything was possible. Everyone had complete freedom to study what they were interested in, and there were just so many talented people around. If you came across something you didn’t know, then your neighbour in the lab next door might know it. Or you would go for lunch and meet someone there, discuss your problem and come back with the answer.

Coming from an Italian university, where the budget was always tight, the IMP felt a bit like the land of milk and honey. There was this store at the basement, and if you wanted to do an experiment in the middle of the night and were lacking an enzyme, you could just godown and buy it. Any restriction enzyme, even the most exotic stuff, was available day and night. I was so impressed.

The other great thing was the quality of the services. When I needed a primer, it was synthesized overnight and I could pick it up the next morning. The entire place had such a motivating kind of energy! We were keen to work on Saturdays and Sundays as well because we got sucked up by that energy. And the people who were new to the IMP, who had just arrived, they were swept along by this avalanche of knowledge. In those days, there was no other place in Vienna like the IMP.

That sounds like you were working day and night back then.

Life was intense, but it was fun. No-one forced us to work like crazy, we were just so motivated. And after work, we would meet in the cafeteria and chat or go out to eat. I must add, we also celebrated the wildest parties at the IMP, they were legendary. ‘Work hard, play hard’ describes it quite well.

In 1999, you became Assistant Professor at the Department of Dermatology of the University of Vienna Medical School. Was it a big change?

When I started my lab at the university, it felt like I was back to reality. The level of bureaucracy was almost as complex as it had been in Italy. When I ordered equipment, it took so long to arrive that I had forgotten about it altogether or had bought it with project funds in the meantime. But times have changed and things are much better now.

How did your career progress from there?

In 2002, I earned my habilitation and became Associate Professor. The institute, which was previously located at the outskirts of Vienna, moved to a more central location in the ninth district, close to the general hospital AKH. Five years later, I became Full Professor for Cellular and Molecular Tumorbiology at the Institute for Cancer Research at the Medical University of Vienna. Since 2010, I am head of the institute which used to be part of the Department of Medicine I but is now a center of its own.

So, apart from pursuing your research, you were able to shape the working environment.

When I took over as head of the institute, it was already very well organized, with sufficient administrative support for the scientists. What was missing were centralised scientific services which I then introduced. I established a FACS-facility, an imaging facility ... and I modelled them after the IMP, where this concept had worked so well. I often had to fight for my ideas. When there were funds available, the general reflex was always to hire another student or postdoc. In the end, these students and postdocs would spend half their time for administrative tasks. So, I started lobbying for support personnel and telling everyone what I had learned at the IMP: that these people make life easier for the scientists and improve the overall performance of the institute.

How is your time divided between research, teaching and administration?

I would say, until three years ago it was 60:20:20, but now it’s more like 40:20:40. I was elected as Chair of the MedUni Vienna Senate in 2019. Leading this governing body has been an interesting learning experience. You realize, a University is not a fast Ferrari that is easy to steer. It is a heavy ship, and moving things is slow, but you can move them. I think it's important that people with ideas and with performance-oriented concepts get involved. Researchers often avoid such administrative positions, but I think it is also important to invest the own knowledge and experience to improve the overall quality for better science of future generations.

You were also involved in setting up the Comprehensive Cancer Center CCC and you are currently its interim head. What exactly is the CCC?

The Comprehensive Cancer Center was modelled after the definition by the NCI and encompasses research, teaching and patient care in oncology. In our case, it isn’t a physical building but more like a virtual center. In 2010, all cancer-related activities at the MedUni Vienna and the General Hospital were bundled under the umbrella of the CCC. The idea is to bring research scientists and clinicians closer together and translate our findings from basic research into clinical practice for the benefit for patients.

What are your current research interests?

In a way, they are still the same. I continued my research on the EGF-receptor and, being surrounded by immunologists, also turned my interests to dendritic cells and immunomodulation in cancer. At some point, I thought of dropping the EGF-receptor, but then we discovered something interesting: in certain tumours, the EGF-receptor is upregulated in macrophages where it plays a tumour-promoting role. That was exciting and is the reason why we are still very much interested in EGFR signalling. There is still a lot to discover!

Interview by Heidi Hurtl, published summer 2022