Jakob Fuhrmann

You are Austrian and studied in Vienna before joining the IMP as a PhD student. Do you remember when you first heard of the IMP and how?

I remember back in the days when I was a student, the IMP had a strong reputation for doing high-end research. I was familiar with its top-level science and the ground-breaking work being done there. My peers and I considered it “the place to be” and best place in Central Europe for cutting edge research opportunities and scientific excellence.

You joined Tim’s lab in 2006, when it was in full swing, but still relatively young. Tim had become group leader at the IMP about four years before. What was his lab and the structural biology scene around him like at the time?

The group was still in its infancy. Cryo Electron Microscopy was not as prominent on campus as it is now. At the time, crystallography was at the forefront, and this was Tim’s expertise. He built all the infrastructure and pioneered the method at the IMP. Tim’s group was also a bit of an outlier in terms of its research focus, because it mainly worked on bacterial proteins. Back then, Barry Dickson had taken over from Kim Nasmyth as director at the IMP, and neuroscience was very prominent. The only other lab doing work related to ours was that of Tom Marlovits [group leader jointly at IMP and IMBA from 2005 to 2017].

I remember the application process for my PhD very well. During the interviews with different principal investigators, I was intrigued by Tim’s excitement, which was a driving force for me to join his lab. He immediately gave me a tour of his lab with a sparkle in his eyes; a lot of his excitement was contagious. I liked the spirit of his high-energy group. When I started, we were maybe five people. I visited Tim during one of the PhD symposia not long ago and the difference in the lab size compared to 2006 felt crazy.

Tim’s lab and Emmanuelle Charpentier’s lab [group leader at the Max Perutz Labs from 2002 to 2009] had a joint WWTF project grant and the plan was to identify and characterize novel antibiotic targets by evaluating the bacterial Clp chaperone system, a protein degradation machinery similar to the eukaryotic ubiquitination system. Several people were working on this project–it was early days for Emmanuelle’s lab as well, and shortly before she started working on CRISPR.

Only two years into your PhD, you won the highly competitive Rabitsch Award. How come?

The key was the first-time discovery of arginine phosphorylation in a protein context, and characterising McsB as a new class of protein kinase. Initially, I worked on McsB as a potential Clp adaptor protein. However, the adaptor function was very elusive and even more intriguingly, McsB had a very mysterious kinase activity, which could not been explained with standard methods. Together with Andreas Schmidt in the proteomics facility, we were able to map the sites of phosphorylation and what other substrates it phosphorylated. We also elucidated the structure of one of the substrates, the heat shock regulator CtsR, bound to DNA. This crystal structure revealed a crucial Arginine residue essential for DNA binding, which became a prime site for arginine phosphorylation, thereby preventing DNA interaction. I still remember sitting with Tim in front of the computer, staring at the electron density map of the Arg62 residue and its perfect position within the DNA minor groove. It was a great moment to connect the newly identified arginine phosphorylation to a mechanistic understanding of its functional impact. The initial findings were published in the journal Science in 2009.

Was there anything you found challenging during your PhD?

Working in science is always challenging and resources are often limited. I had done my master’s thesis with Baxter, so by the time I started at the IMP, I was used to corporate settings in addition to university environments–this certainly made the transition to the IMP easier. I would consider the IMP a privileged research institute with industry standard facilities and support units, including access to extensive material supplies. However, there are always unknowns. The real challenge was probably starting a new research project with limited prior assay and reagent availability, as well as working on mysterious kinase activities that could not be explained with current methods. To overcome all these challenges, I really had to start thinking outside the box and try out completely new approaches. I simply followed my curiosity and the science; and did my best to be persistent. Moreover, state-of the art facilities such as mass spec and bioinformatics at the IMP provided great backing for all my work.

You stayed at the IMP until 2011, published extensively, and then moved to the Scripps Research Institute in Florida for a postdoc. Why the Scripps? And how did it differ from the IMP?

My goal was to go to the US to experience its academic system, do a postdoc with a high-reputation organisation and learn first-hand how things are done there. Initially, I applied for positions in Boston and New York, visited labs and explored possible research projects. There are two ways to go about a postdoc opportunity: by staying faithful to either your methods and skillsets, or to your research questions. I chose the latter since I wanted to expand my skillset to chemical biology, and decided to keep my subject and apply methods that were new to me. Scripps had a fantastic setup for chemistry and the methods I needed to further elucidate the impact of protein arginine modifications, offering me the best conditions.

Scripps’ main campus is in La Jolla in San Diego, but I went to the Florida site, which at the time was a new campus with everything shiny and brand new. I had a great and very productive stay there.

The next big change came when you transitioned to industry, joining Genentech in San Francisco in 2017. Can you describe your role and how it changed over time?

In every scientific career, finishing a postdoc marks a turning point with a crucial decision to make: do you want to stay in academia or move to industry? Initially, I only considered academia and successfully applied for several assistant professorships around 2016, receiving multiple offers. However, the funding situation was really tough at the time, particularly in the US. With this challenging funding situation in mind I found industry very appealing. Genentech, in particular, has a strong focus on publication and exploratory research, which made it an attractive option to combine research with commercial applications. Genentech was the only corporation that I considered.

After joining Genentech, I started by setting up a small group. In general, it felt very much like research in an academic setting, but with stable funding and exposure to a drug development pipeline. Ever since, my work has gone beyond mechanistic research, and I discovered–with a bit of surprise, to be honest–that I really enjoy the applied science side. It allows me to make a difference and apply our great scientific insights into drug development, ultimately helping patients.

In academia, I always thought industry was a different world, but the difference is gradual. Exploratory research and applied research continue to come closer to one another. Industry and academia are no longer as distinct as they may have been some 20 years ago, and more and more collaborations are starting to emerge.

Genentech is a co-founder of the IMP – have you ever come across this in the company? Is there any awareness left for this?

It’s funny, but when I presented Genentech as a co-founder during a symposium at the IMP in 2019, very few people in the audience were aware of this. Similarly, I have only come across a couple of people here at Genentech, those who have been with the company for 30 years or more, who still know about it. And they are becoming fewer.

How much of your IMP experience do you still apply in your job on a regular basis – if any?

I strongly believe the curiosity part of me was shaped by the IMP, along with persistence – staying focused on your target, and working hard towards your goal. This mindset, influenced by the scientific drive at the IMP, continues to guide me. Additionally, the emphasis on teamwork, both within Tim’s lab and beyond research groups, particularly with mass spec, is something I learned at the IMP and still apply regularly in my job.

Are you still in touch with IMP colleagues past or present?

The last time I was at the IMP was for the Vienna BioCenter PhD symposium in 2019, before the pandemic. I used to visit more frequently until then. I am still in touch with Tim and other peers from the lab. Things got disrupted due to the pandemic, but I hope our encounters will become more frequent again in the future. I fondly remember the great social activities, such as the annual ski trip, summer sport festival, and particularly the fantastic experience of dragon boat racing. The IMP team, “IMPerfectos”, won the dragon boat trophy in Carinthia, it was amazing. I think the motto “work hard and play harder” perfectly captures the sentiment of that time.

If you had to send a short piece of advice to current PhD students at the IMP, what would that be?

The transition to industry is not a one-way trip. Although I am quite focused on a late stage-research project right now, there are always opportunities nowadays to return to academia. Scientists today, and especially students, should not think in predetermined categories. There is more fluidity than ever before. This is probably even more true in the US, where people often have a stronger “just do it” attitude. People here are less bound to traditional patterns, although to be honest, the IMP had that attitude as well to some extent.

Published in 2024.