Pacesetter for the life sciences

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Four decades of top-level research in the life sciences: the Gene Center Munich celebrates its 40th birthday on 24 June. Founded in 1984 as a joint institute of LMU and the Max Planck Institute of Biochemistry, it combines interdisciplinary research with the fostering of early-career scientists in key areas of the life sciences and shapes the life sciences in Munich and further afield. Professor Karl-Peter Hopfner has headed the center since 2015.

What’s special about the Gene Center?

Karl-Peter Hopfner: On top of its mission to strengthen molecular biology in the German research landscape, the Gene Center Munich has had two other main features since its foundation. One is its strong interdisciplinarity, which we encapsulate in the slogan, “Beyond Disciplines.” Thanks to its special organizational structure, the Gene Center has the capability – outside the classical faculties – to create links between faculties and bring expertise from different fields together in one building.

The second feature is the center’s leading role in promoting early academic independence. Just as important as interdisciplinarity, this feature has been there from the outset. The fostering of early-career research groups began with the establishment of the institution and was further developed in the so-called tenure-track model, which enables researchers to be appointed to a professorship directly after the postdoc phase – bypassing the traditional habilitation. This appointment is then made permanent following an evaluation.

We have maintained and expanded these two emphases over the past four decades and they will remain the lodestars for the Gene Center in the university landscape of the future.

What was the goal when the Gene Center was founded?

Hopfner: At the start of the 1980s, when molecular biology was an emerging discipline, Ernst-Ludwig Winnacker and colleagues realized that it would not only open up groundbreaking new research possibilities within the life sciences, but also pave the way for exciting medical and industrial applications. Our center is one of four centers that were founded back then as part of a nationwide gene center program designed to keep and establish this fledgling technology in Germany and recruit young researchers for this purpose. These centers were called “Gene Centers” at that time and, in our case, the name stuck. The founding name of the institute was the Laboratory for Molecular Biology.

It was established in 1984 under founding director Ernst-Ludwig Winnacker as a joint institution of LMU and the Max Planck Institute of Biochemistry, in the premises of which the Gene Center was housed for its first ten years, before our building on Campus Grosshadern was inaugurated.

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What are your main research areas?

Hopfner: We have three mainstays: One is basic research in the life sciences – that is, the question as to how cells and the molecules in cells work.

The second mainstay has developed over the past ten to fifteen years. This is the domain of molecular systems biology, in which we investigate how molecules cooperate to form living systems. Molecular systems biology encompasses fields such as gene regulation, the immune system, cell-cell communication, and cell differentiation.

In the first domain, then, we have a highly focused view on molecules as soloists, so to speak, whereas in the second domain we take a broader view on the orchestra of many molecules.

The third mainstay is clinical translation, which involves groups from the clinical sciences, from LMU University Hospital, and from the Faculty of Veterinary Medicine. The focus here is on taking the findings from research and developing them with an eye to therapeutic applications.

Looking back on the history of the Gene Center, which events shaped its development?

Hopfner: After the foundation and the first phase in the Max Planck Institute of Biochemistry, the construction of our building in 1994 was certainly a milestone – and a significant event in the development of Campus Grosshadern as well. Apart from LMU University Hospital Grosshadern and the Max Planck Institute, this was all just fields and farms. Then came the Gene Center, followed by the chemistry buildings, the biology buildings, and the Biomedical Center. All that developed around the Gene Center to an extent. And now we have this wonderful campus, which is one of a kind in the life sciences in Germany. The Gene Center played a pivotal role in shaping this evolution.

Another important development was the idea of Rudi Grosschedel, who headed the Gene Center from 1998 to 2003, to establish the tenure-track model, inspired by his experience in the Anglo-American academic sphere. I think that was a brilliant strategic move, including on the part of the university and the faculty, who all pulled together to make it a reality. It has really helped us be competitive in the recruitment of excellent researchers from all over the world over the past 20 years.

How does the story continue?

Hopfner: Further milestones are related to the excellence initiative. In this context, Patrick Cramer in particular hugely expanded top-level research at the Gene Center from 2004 to 2013. Together with colleagues from the chemistry faculty, we founded the first cluster of excellence in the form of CIPSM (Center for Integrated Protein Science Munich). This was an important step for the Gene Center, and later we had a Collaborative Research Center funded by the German Research Foundation, where we demonstrated that we could pursue excellent joint research here.

In the next round of the excellence initiative, Ulrike Gaul, who came here as a Humboldt Professor in 2009, worked very hard with Patrick Cramer to establish systems biology at the Gene Center and organized the QBM graduate school, which bridged biochemistry and physics.

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And then BioSysM came along later?

Hopfner: Yes, we grew so much over time that it was getting cramped here. And so Patrick Cramer led an initiative together with Ulrike Gaul to apply for an extension – what would become BioSysM (Research Center for Molecular Biosystems) – which was inaugurated in 2016. Through the establishment of BioSysM, we gained a second axis, as it were, which principally covers the field of molecular systems biology. Meanwhile, structural biology and translational research are mainly located in the original Gene Center. The art of course is to synergistically expand and bring together these different research strands.

Is it accurate to describe the Gene Center as an incubator for interdisciplinary collaboration?

Hopfner: Indeed. One strength of the Gene Center is that the whole is greater than the sum of the individual parts. Naturally, this only works if there are synergies and people work well together. We have a relatively large number of publications that were produced by multiple groups. When you appoint people and see that three years later, they publish a joint paper that is celebrated by peers, what more do you want?

Interdisciplinarity was always very important to me, and it’s a quality that’s baked into the Gene Center. By virtue of the groups here with members from four faculties, you can say we live the interfaculty creed, and this gives rise to a plethora of collaborations. Moreover, it’s something I’d like to further expand.

Are there synergies in teaching as well?

Hopfner: Yes, we’re very active in this regard. Together with the Department of Chemistry, we have a bachelor’s degree course built on a so-called Y-model. The students start out together and branch off later, either in the direction of chemistry or of biochemistry. This is a unique course in the German research landscape, one that has many USPs and is highly attractive. We’re currently thinking about expanding this portfolio with somewhat more specialized bachelor’s degree courses. We also want to forge new paths here – for example, by connecting systems biology and biochemistry.

In addition, we have an international master’s degree course in English, where 40-50 percent of students come from abroad. We also help our students in the master’s program get to know the world – say, by doing their thesis abroad. This is a great and relatively straightforward opportunity to experience research in a different country.

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Can you name examples of innovations that were developed at the Gene Center?

Hopfner: My favorite example comes from the Klaus Conzelmann group, which worked on viral systems. These included rabies viruses, which attack nerve cells. The group developed a system whereby the viruses, by means of a fluorescent dye, stain the cells they attack – along with all the cells directly connected to them. In this way, scientists can visualize how these cells interact in the brain. This was a stunning achievement and the system is used by neurobiologists worldwide to map how nerves are configured in the brain.

Another brilliant innovation from the Gene Center – and one that may not be on people’s radar – was developed by Johannes Söding and staff and actually comes from the field of computational biology. Söding’s team developed a method for comparing amino acid sequences and searching for weak homologies – that is to say, distant relationships – making it possible to construct very large relationship maps across all known life forms. This technology was instrumental in the development of the AI program AlphaFold2. These types of AI models, which can not only predict the structure of proteins, but also generatively design them, are partly based on analyses made possible by the technology created by Söding and his team.

And then of course we’ve done a lot of spectacular things in basic research – in areas such as transcription machinery, ribosome biology, the innate immune system, DNA repair, mitochondrial stress, and chromatin. Now, these are not classical innovations in the form of patents, but they are science that will make its way into the next generation of biochemistry textbooks. These are our two spheres – basic research and applied research.

No doubt, the technological possibilities have also changed hugely over the past 40 years …

Hopfner: I don’t need to go back 40 years for that – even over the last four years, the world of research has dramatically changed. Rapid technological advances will undoubtedly transform our work in the future, opening up brand new possibilities. I must say that many researchers at the Gene Center were way ahead of their time. For example, we had scientists working on gene therapies and protein design and protein folding. These were wonderful projects, which were not really effective at that time in the late 90s because certain technological advances had not yet been made. The scientists couldn’t work with the accuracy of structure prediction required for protein design, for example, or the methods of gene therapy weren’t yet accurate or efficient enough.

But these fields of technology and development are coming back strong – for example, as a result of CRISPR/Cas9. Gene therapy is currently one of the fastest developing therapeutic approaches alongside mRNA technology.

And protein design has also progressed thanks to generative AI. The AI model AlphaFold and AI developments in protein design will open up whole new worlds, including in the therapeutic sphere and in biotechnology. This rapid progress is also a big challenge for an institute like ours, because naturally you have to plan ahead a bit. Our strategy is to set ourselves up on a relatively broad technological basis, so that we can pursue as many directions as possible, and embed the whole in a research topic that binds us together.

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Which topic will provide your collective superstructure in future?

Hopfner: Nucleic acid biology, which has seen huge advances in recent times. First of all, the study of nucleic acids – that is to say, RNAs and DNAs – looks at fundamental processes in the cell. This includes how nucleic acids work in the cell, how proteins bind to them, and how DNA damage and diseases arise. Secondly, nucleic acids, particularly in the form of RNA, have become a therapeutic entity and are currently at the heart of much translational research. That’s why they’re an important topic here at the Gene Center.

What is your vision for the future of the Gene Center?

Hopfner: To build on our motto “Science Beyond Disciplines.” We want to introduce more AI so that we can participate in fields such as generative AI and design. If we achieve this and are attractive to talented people from all over the world thanks to our flat hierarchies and interdisciplinarity, then we will be in an excellent position over the years to come as regards pursuing top-level research.