Frank Schnorrer studied Chemistry and Biochemistry in Würzburg, Tübingen and Munich. He completed both his diploma and PhD in the lab of Christiane Nüsslein-Volhard at the MPI for Developmental Biology in Tübingen. In 2003, he joined Barry Dickson’s group at the IMP as a postdoc and was part of the pioneering team that set up the RNAi fly library. From 2008 to 2016, he was an independent group leader at the MPI of Biochemistry in Martinsried. Since 2016, Frank has been a senior group leader at the Institute for Developmental Biology in Marseille.
You studied Biochemistry at the universities of Würzburg, Tübingen and Munich. How and when did you come across your model organism Drosophila?
I actually started with chemistry in Würzburg, so I was solely fascinated by the smell, the colours and of course the “power” of the most aggressive compounds to create blasting effects. I thought at that time that biochemistry was just a continuation of organic chemistry with some sort of DNA touch to it. Obviously, I had no idea about proteins and that enzymes do not need to be heated to 200 degrees to perform amazing chemical reactions.
However, the biochemistry institute in Tübingen was very traditional at that time and was mainly focused on purifying proteins and measuring their activities. It was only after I started to work as an undergraduate in Christiane Nüsslein-Volhard (Janni)’s lab at the Max Planck Institute for Developmental Biology that I was introduced to the beauty of molecular biology.
Of course, there was also Drosophila – Janni had just received the Nobel Prize for the genetic control of fly development the year before. I made embryonic extracts and was fascinated that a kinase isolated from wild type embryos was active in a biochemical assay, but was inactive if isolated from mutants (of the Toll pathway). This was my first exposure to Drosophila genetics, and I loved it. I did a one-year internship at the Max Planck Institutes in Munich, but planned to continue with flies in Tübingen for my diploma thesis. As this went well and I finally learned genetics from another PhD student, Stefan Luschnig, Janni allowed me to stay as a PhD student, studying mechanisms of mRNA (bicoid) transport to one end of the developing oocyte. This was the time when GFP was discovered, and I was able to record the first videos of cytoskeletal proteins and investigate their dynamics in oocytes.
From 2003 to 2007, you were a postdoc in Barry Dickson’s lab at the IMP. What project did you work on?
I was looking for a system in which I could best combine imaging with genetics for my postdoc and thought the large muscle cells of the fly embryo would be ideal. Surprisingly, Barry allowed me to work on that, despite having nobody else in the lab interested in muscles. I did a classical mutagenesis screen and found a cool mutant that we named kon-tiki, the gene coding for a receptor required for the recognition of tendon attachment sites in the developing muscles.
And so I was connected to the axon guidance crowd in the lab. But this crowd was shrinking as the new hype was behaviour. The big goal of the lab was to develop a tool that could test for a role of any gene in any neuronal type, ideally in an inducible manner. With the discovery of RNAi, that suddenly seemed feasible, and under the heroic guidance of Georg Dietzl in Barry’s lab we generated a genome-wide inducible transgenic RNAi fly library of more than 20,000 different fly strains, the basis for VDRC. I was able to use this library to test for gene function in muscle and suddenly also do behaviour. I tested to see whether the flight muscles still powered flight after gene knock-down. Together with Georg and many other colleagues, we performed over 25,000 flight tests, collecting all the flies in the same hoover after the test.
How did your time at the IMP shape you as a researcher, and what did you get out of it?
I still remember my first weeks at the IMP – I immediately felt the special dynamism in the air. The institute was super-crowded and we were continuously bumping into each other. The waiting list for desks was long, and I started with a shared bench in Barry’s lab, not even thinking about a personal fly station. Everybody was working towards her/his next "Monday seminar" – 20 minutes that decided whether your last year was any good.
This made for an amazingly interactive atmosphere. Obviously, my topic was only one of many fascinating problems in nature, and it taught me to constantly question if this is the most exciting thing you want to study, or as Kim used to put it: "what you really want to find out is…"
I loved this culture of discussion and the social bonding within the institute. Barry was a demanding boss who taught me to ask the big questions. "Don’t be scared if others say this cannot be done within a reasonable time frame! Work together with the best people in the field to be maximally synergistic!" The IMP facilities enabled us to be maximally efficient, but since time was limited by fellowship duration and other constraints, you’d better use your time wisely. I learned how to coordinate large tasks and how to collaborate with people, and I worked with my first diploma student, Irene Kalchhauser, who is still working in science today. So the IMP really provided me with everything to get mentally ready to run a group in the future, and I aimed to find a similarly vibrant place and applied to Max Planck.
Can you briefly describe how your career developed after you left the IMP?
I held an "independent" Max Planck group leader position for nine years. These positions were centrally selected and you could choose which institute to join. I chose the Biochemistry Institute in Munich, not only because of “Mia san Mia” FC Bayern, but largely because I found a complementary hosting department, with a very supportive director, Reinhard Fässler, studying integrins and forces – a perfect environment for muscle developmental biology. Our Drosophila strains were the first this famous institute had ever seen! Quite a challenge, but the neighbouring Neurobiology MPI hosted various fly labs, so we managed to arrange a shared fly kitchen and joint fly seminars.
I was very lucky to recruit excellent PhD students who got our lab off the ground. My first one, Cornelia Schönbauer, moved with me from the IMP and we explored the fruits from the large RNAi screen together.
The quantitative mindset of the Biochemistry institute and our department in particular enabled us to branch out and study muscle development with a much more quantitative mechanobiology focus – this is still one major focus of my current lab. Again, this exciting evolution worked successfully thanks to the considerable number of synergistic collaborations with many colleagues over the years and the daily input of seminars and lab discussions.
Your CV reads like the picture-perfect career of a researcher. What were the most challenging times in your professional life?
Perfect career? Well, my first mistake was to not insist on being last author on the big RNAi screen paper. Of course, we started this at the IMP, but published it only in 2010 after working with my small group for two years with myself as first author and Barry last. The effect was that my EMBO Young Investigator application was rejected and I was devastated. A year later, the paper from my first PhD student was under review and re-review at Science for 15 months before it got rejected! I was despondent again and questioned the entire publishing system. However, of course, the review process made the paper better, and within three months it was published in Nature. This was the game-changer. Suddenly EMBO-YIP worked out and my ERC was funded. Of course, we did the same science as before the editor decided to accept the paper.
A further major struggle was the Max Planck group leader system. Generously funded, the group leader gets a five-year contract, which after four years is potentially extended for two more years, and then again for a further two years if you’re lucky. So the pressure remained high; my staff and myself were constantly on short-term contracts, knowing that tenure is no option. This was my third unhappy phase, which lasted a bit longer. Once, a famous American professor visited my office and asked “when do you get a REAL job?” I don’t remember what I said to him in reply.
Shortly after, I found the love of my life (she actually graduated with Hartmut Beug before my time at the IMP) and I was able to convince her to give up her fabulous Max Planck funds and move with me to southern France!
You are now a senior group leader at the IBDM in Marseille. How do life and work there compare to your previous affiliations?
Many people ask me why I chose France. I hadn’t considered France for many years, not knowing the French system and not being able to speak the language. My lab was quite shocked when we opted for Marseille and not for well-funded Switzerland.
I work at the Developmental Biology Institute Marseille, a CNRS-funded institute (CNRS is the French Max Planck equivalent, but much less well funded) and I’m also affiliated with Aix Marseille University. I always liked to give lectures and have contacts with young undergraduate students. The teaching workload for CNRS researchers here is minimal, which means that I can focus entirely on my group and our research. We have more than twenty groups at our institute, eight of which work with the fly model. This means that we’re at the heart of fly research in France! Mechanobiology, with its emphasis on interdisciplinarity, is a very important focus and fits our research perfectly. The recently founded Turing Center (http://centuri-livingsystems.org/) is bringing scientists from different disciplines together to study important questions of life in a quantitative manner, a perfectly suited environment for us!
The CNRS system funds all group leaders permanently, so there’s no stress with endless applications for the young group leaders – a great bonus that creates a very relaxed and pleasant working atmosphere at our institute. On the other hand, core funding is minimal and we keep on having to tap into multiple available funding sources for grants. I was lucky enough to recruit a fantastic postdoc, Nuno Luis, who also managed to secure a permanent CNRS position. This means that he is now also a CNRS researcher and we can collaborate long-term. This enabled us to branch out further and we started to tackle the important problem of muscle ageing. That’s how the CNRS system works, although I’m still at the very beginning…
Life in Marseille is fantastic. Our institute is in the Calanques national park, a rock climbing paradise, and you can improve your skills daily with stunning views of the Cote d’Azur just 15 minutes from the lab. The food and wine culture is amazing, almost like back in Vienna.
Interview by Heidemarie Hurtl, 2018
Alumni Stories: quick links
Angelika Amon - Jörg Betschinger - Sarah Bowman - Martin Breuss - Rafal Ciosk - Greg Emery - Giorgio Gilestro - Silke Hauf - Christian Häring - Konrad Hochedlinger - Andreas Hochwagen - Andrea Hutterer - Claudine Kraft - Christoph Lengauer - Marieke von Lindern - Stephen L. Nutt - Snezhka Oliferenko - Bernhard Payer - Mark Petronczki - Silke Pichler - Kanaga Sabapathy - Walter Schmidt - Georg Schneider - Frank Schnorrer - Philipp Selenko - Camilla Sjögren - Andrew Straw - Giulio Superti-Furga - Attila Toth - Tomyuki Tanaka - Frank Uhlmann - Hartmut Vodermaier