“I have great expectations for biosciences to be the big player of our century”

Driven by a fascination for mathematical and physical concepts, Gotthold Fläschner ventured into biosystems research for his doctorate. What looked like “smooth sailing” in the beginning turned out to be rather challenging. Now, Gotthold was awarded the ETH Medal for his outstanding dissertation. In an interview, he elaborates on the ups and downs during his PhD, his decision to move into industry and why he considers D-BSSE a “very stimulating melting pot”.

by Carolin Arndt Foppa
Fläschner-Gotthold_D-BSSE-doctoral-defense

When you were a school boy, you dreamt of becoming a Professor of Mathematics. In fact, you started studying mathematics and then moved into physics. In particular, you were fascinated by teleportation and quantum mechanics, so, your passion was in theory and mathematical concepts. What made you transition to biosystems research?

Several things, actually. I felt intrigued by the complexity of biological systems. There is a lot to be explored from the physics’ side. I was hoping to understand where I could bring into biology my passion for theory and mathematical concepts. At the same time, I was looking for ‘real-life’ applicability. Typically, that is tricky because the higher the applicability, the lower the chance of mathematically appealing concepts behind, simply due to their complexity - at least in my experience. I am constantly looking for this sweet spot where appealing concepts meet application. Also, I have great expectations for biosciences to be the big player of our century. And, to be part of that adventure, I went into biophysics for my PhD.

You completed your doctoral project after six years of research in the Biophysics group led by Daniel Müller. Your research findings were ground-breaking for the entire discipline, and your thesis was honoured with the ETH Medal for an outstanding dissertation. What exactly did you find out, did it all go after plan, and what drove your motivation?

The idea was to measure the mass and later mechanical properties of single cells. When I joined, the project was already going on for some time. Daniel had hired a postdoc, David Martínez-Martín, to come up with a way to measure cell mass. Some time later, they were looking for a PhD student with excellent knowledge in physics. My skills were a perfect match for that project - I am even today surprised, how lucky that was - and as I was fascinated by the idea of the project, I joined. In the beginning, it looked like smooth sailing for me. I remember David saying one evening, I might be able to do the fastest PhD ever. This did not really become true, partly due our high ambitions, but also because we ended up grappling with many issues – for instance, cell survival. And once we achieved cell survival, we performed a series of very challenging experiments. Yet, we never published them, as our control experiments did not confirm them. That was harsh. So, we needed to explore new directions, and this repeatedly. Thankfully, Daniel was quite patient and persistent. Ultimately, we were able to perform fast and high-resolution cell mass measurements under cell culture conditions. We found mass fluctuations in the time scale of seconds that were actively driven by the cell and were probably a result of mass regulation. We saw how the cells accumulated mass on the long timescale and how it stopped once we had infected them with a virus. After that, I tried to extract mechanical information from the cells using the same device. Initially, it was unclear how to do that. So, I was happily deriving formulas and performed computer simulations to find a way. The results I finally was able to extract, showed cell mechanical properties on different timescales. Understanding these time-dependent properties can tell us how the structure of cells shapes their properties and behaviour. This is reported in our most external pagerecent paper published by Nature Communications.

Many students don’t know if a PhD is the right choice for them, maybe you can give some advice? Starting with you: Was doing a PhD the perfect choice for you and if so, why?

{laughs} To know whether it was the perfect choice, I would have to go back to quantum mechanics, invent something to talk to the centillion versions of myself in the parallel universes and compare notes. No, for real, I think my first advice is don’t bet on doing the 'perfect thing', but find something '(really) good' and embrace it until you go for the next thing. Nothing will be perfect. If you choose to do something, you choose not to do many other things - that is not easy. Also, things that you think are worth achieving, are not easy to have by definition - so it will be hard. I think you should try to make the best-informed decision you can make, try to research your choices and your preferences the best you can. That way, you have a good chance of getting what you want and forgive yourself if the choice turns out to be bad. In case you can't improve a bad situation, quit rather sooner than later. Such quitting is not failing, in fact, it takes a lot of insight and courage. - But to say something more specific on whether or not to do a PhD: I think you should be interested in science and technology and ideally full of awe for the crazy stuff all around us and what might be possible!

In your PhD, you pioneered an approach to measuring mass at picoscales, and you are co-inventor on several patents surrounding this measurement and another one. You then developed a technique to measure cell mechanics on the same mass measurement device. You are a real innovator! What is next, have you given some thoughts to the commercialising of the patents?

To be honest, I was never really interested in patents as such. I was more interested in doing the science, and it was a welcomed by-product that patents arose from this work. I was lucky in that sense. Then, ETH licensed some patents relating to the 'pico-balance' to the swiss company Nanosurf. Obviously, I liked the idea that our research would find such a great way into the science community. Nanosurf and our group started to collaborate from thereon, and I got involved. After I finished my PhD work, Nanosurf approached me and I accepted their offer to work there as a project manager.

At Nanosurf, you will help develop a commercially attractive product that allows cell mass and mechanics measurements. What guided your decision to work for industry, what are your expectations?

The decision was not easy, and I see it as an experiment that promises good outcomes. I am very interested in an academic career, yet I have a good idea about the rocky way that would lie ahead. At the same time, the industry has its appeals too, and I do not know anything about that particular career path. So, I want to get some experience, collect insights. That makes sense to me, in particular when I consider what I want: impactful, intellectual challenges and my freedom to engage with them. In all these regards, I believe that Nanosurf is a great place to be. Also, they have ambitious plans and I like to see how the project that I know for so long can grow further. So, I am in good hopes that I find something that suits me in industry. And if it does not suit me, I certainly will learn for my next steps and be productive while doing so.

In retrospective, it looks like you had a stimulating time at D-BSSE. If a potential PhD student asks you, how would you describe the department?

That is a difficult question to answer, because the experiences are highly individual. I would probably compare my experience with the D-BSSE to a rip current - a strong water current. If you want to ride it and eventually master it, it will get you out to the sea, where you can surf the waves. But you need to be careful, it can be rewarding but not without the risk of peril. To give one illustration, within the D-BSSE you have people with highly heterogeneous backgrounds, culturally, professionally and mentally. This makes for a very stimulating melting pot, but it can also bring problems. Also, D-BSSE constantly strives for international recognition and excellence, and does successfully so. There are evidently two sides to this coin. Particularly in the recent years, I was glad to perceive the department as a place, where PhD students did not only engage in matters of departmental relevance but where student involvement was also asked for. As a student, I was in plenty of meetings with the department leadership to understand what is working well in the department and what needs improvement. It takes time and effort, but you can make it worth it. To summarize, I think D-BSSE is a place where you can learn a lot about science, have the chance to do great research and also grow personally.


Thank you, Gotthold, we wish you an exciting journey into the private sector and hope to hear again from you soon. Stay in touch!

 

Find the doctoral thesis of Gotthold Fläschner (2019) Mechanical oscillators probing cell mass and mechanics.

Gotthold's most recent publication: Fläschner, G., C. I. Roman, N. Strohmeyer, D. Martinez-Martin & D. J. Müller (2021) external pageRheology of rounded mammalian cells over continuous high-frequencies. Nature Communications, https://doi.org/10.1038/s41467-021-23158-0

Learn about the Biophysics group led by Daniel Müller.

More information about external pageNanosurf.

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