Each cell of a multicellular organism contains the entire genetic code for that organism, but not all of those genes are active in every cell. The regulation of gene expression gives rise to different cell types with specialized functions and controls organismal development. Even after a gene has been transcribed, its expression can be regulated by a variety of mechanisms at the level of the transcript or the protein product itself. At the post-transcriptional level, the control of RNA fate and function is an important layer of gene regulation. The Ameres Lab studies the role of RNA and its modifications in this regulation and how aberrant gene expression contributes to human disease.
Stefan, you first joined the Max Perutz Labs, for your PhD studies, at a time when the institute was newly founded. Now, over a decade later, you have returned as a group leader and professor. What´s it like to now be among the “seniors”?
Well, obviously time is flying and I guess it makes me realize that I’m getting old. But beyond that I’m of course very happy about the opportunity to be able to return to the Max Perutz Labs in my new position. I certainly have great memories from my time here as a PhD student. I am particularly excited about the possibility to provide to the younger generation the support and mentorship that I enjoyed in the past here at the Perutz. Particularly, I am really looking forward to many scientific interactions with my colleagues and I hope that in the future we will be able to further contribute to the established status of Vienna as a hotspot for RNA research in Europe and beyond.
If you look back even further, when and why did you decide to become a researcher?
I think that my interest in understanding molecular mechanisms in biology was somehow rooted in my upbringing. My father was an entrepreneur in the engineering field, and I frequently helped out to put machines together. My mother was working as a nurse in a children’s hospital. I guess that this somehow set the basis and the boundaries for my interest in later on systematically trying to dissect molecular machines in a biomedical research setting. But of course, on the way there, there were many influential teachers, lecturers, mentors and colleagues that had an immense impact on my passion for science.
I noticed the guitar in your office so I wondered if music was a career you ever considered?
[laughs] Well early on, sure, but then recognizing my limitations made me choose wisely on my future career. But it’s certainly still a hobby that I have and looking back to my PhD times – I think it was a great time to assemble a band of PhD students and even play on the roof of the Perutz Labs, so those are great memories. And maybe who knows if there will be a chance in the future to assemble a couple of colleagues to revive this.
Let’s talk about your research: you did your PhD in the Lab of Renee Schroeder, an expert in RNA biology and now you are focused on the role of RNA modifications in the regulation of RNA fate and function. What fascinates you about RNA?
RNA in one form or another impacts every process in a cell and this is possible because RNA carries out a very broad range of functions. These range from transmitting the genetic information that codes for molecular machines and the structural building blocks of the cell, to the regulation of gene expression during development, cellular differentiation, and in the reaction to changing environments. These broad functions are rooted in the fact that life on earth may have begun with a simple RNA molecule – this is what the ‘RNA world’ hypothesis suggests. RNA combines the ability to both store genetic information like DNA, and drive chemical reactions like proteins. Many of these versatile functions are still found in current biological systems. And in that way one can really refer to RNA as the central molecule of life and, as such, it has surprised many generations of scientists and will continue to do so.
If we focus on the curiosity driven, basic research part – what do you think are the big open questions in your field?
In contrast to what is frequently portrayed as a static picture that many assays provide when inspecting gene expression, the process is actually a highly dynamic interplay of many steps from RNA synthesis to decay. I think that one of the major challenges is to develop tools that allow us to monitor and measure such highly dynamic processes inside living cells. What we do is we really try to develop and employ novel technologies, such as SLAMseq, that allow us to produce molecular movies of gene expression rather than static images with the goal to capture and quantitate such dynamic processes. And with such assays in hand we are really trying to uncover and dissect fundamental biological processes that control gene expression.
Thinking back to when you did your PhD here at the Perutz and with the experience of more than eight years as a group leader, what would you do differently and what is your advice to students?
Honestly, I am not sure I would do many things entirely different, which certainly does not mean I have made no mistakes – I certainly made many of those. I feel I have learned a lot from my mistakes. My advice to students would be to be really courageous and not fearful of what the future may bring. I think this is probably one of the best times to do science, with endless possibilities. While I acknowledge that competition is very high, particularly in the academic setting, I would say that as long as you do what you are really passionate about and what really fascinates you, there will almost certainly be a path forward.
Read more about the Ameres Lab.