STEM field | Insights

Could you please briefly describe your academic career to date? 
In high school, I was already very fascinated by molecular biology and genetic engineering. I had followed some of the work of Craig Venter and the Human Genome Consortium, and I was deeply impressed by the fact that all of nature's astounding beauty and complexity ultimately emerges from a simple molecular language called the genetic code. By the age of 15, I was convinced that I wanted to work in the field of genetic engineering.

My scientific career began in 2006 at the Heidelberg University, where I studied Molecular Biotechnology. At that time, this was a rather new subject and Heidelberg University was one of the few places in Germany to offer it. I chose Molecular Biotechnology because it covered (and still covers) a broad spectrum of topics in molecular and cell biology, chemistry, physics and mathematics, which I believe is an ideal foundation for a future career in the life sciences. 

I then joined the department of Roland Eils, an expert in bioinformatics and genomics at the BIH in Berlin and at that time head of a large department split between the DKFZ and the University of Heidelberg. As an experimental biologist surrounded by mostly computer scientists and theorists, I had a lot of freedom, which I enjoyed very much, but I was also regularly exposed to topics outside my comfort zone. The time in Roland's department was certainly the key to my future career steps. In addition, I was fortunate to meet Prof. Barbara Di Ventura, who was then in Eils' department and later became my Ph.D. advisor in optogenetics, which I completed in 2016.

Instead of going abroad, which is very typical for young postdocs, I stayed in Heidelberg for four more years to start my own group in Eils' department. I was very lucky that the first people I hired were really outstanding students. One of them was Felix Bubeck, then a master's student in molecular biotechnology. He and my first PhD student, Mareike Hoffmann, combined CRISPR gene targeting technology with optogenetics in an innovative way. The resulting paper in Nature Methods and several subsequent papers in high-impact journals laid the foundation for my next career steps. After a short research stay in Pamela Silver's lab at Harvard University, which was abruptly ended by the start of the COVID-19 pandemic, I spent three years as an assistant professor at the Department of Biology at the Technical University of Darmstadt. With its highly supportive and family atmosphere, TU Darmstadt was an ideal environment for me to take the first steps as an independent group leader and professor and to further develop important skills such as grant writing, teaching and administration.

Last year, I was fortunate to return to the Institute of Pharmacy and Molecular Biotechnology as a full professor for Pharmaceutical Biology, the institute where I started my studies in 2006.

What are you currently focusing on in your research work and what advantages does AI bring to it?
The core goal of our research is to develop tools and strategies to precisely perturb and control cells at the molecular level. Currently, we are focusing on the development of switchable proteins, i.e. proteins whose activity can be turned on and off by either endogenous cellular signals, such as metabolites or temperature, or exogenous triggers, such as drugs or light. The core question we are asking is: How can we combine receptor domains that sense certain triggers with effector proteins so that the receptor controls the activity of the effector?

Nature does this protein control beautifully, using strategies based on changes in protein shape and interactions. We are trying to learn from nature using an “understanding by engineering” approach. The natural protein repertoire is vast, comprising hundreds of millions of protein sequences. To make sense of this huge dataset and derive predictions that we can feed into protein engineering, we use AI, in particular large language models trained on protein sequence and structural data. We are also using machine learning combined with model discrimination approaches to understand what parameters we need to pay particular attention to when engineering switchable proteins.

What fascinates you the most about your field of research and how did you become interested in it in the first place?
The field of research in which I work is now at the point where we are moving from understanding cells to engineering them at the molecular level. Cells can be thought of as the most sophisticated nano-robots that exist. These nanorobots can move, store energy, synthesize complex compounds, and most importantly, they can replicate themselves. In other words, they are able to make copies of themselves to a high degree of perfection using simple biochemical compounds as building blocks. 
I find it extremely fascinating that we humans can now program these self-replicating nanobots simply by changing the genetic code. This makes it possible to build new functionalities into living systems whose applications are limited mainly by our imagination.

Why is Heidelberg University the ideal place for your research?
Heidelberg is a truly unique place because expertise from all scientific disciplines is "squeezed" into a relatively small area on the Neuenheimer Feld. This creates an incubator-like, highly collaborative environment where you can find experts in virtually every method and topic - from cell biology and chemistry to physics and engineering to IT and computer science - literally next door. I am also very excited to be part of the Faculty of Engineering Sciences, which is prone to inspire new ways of engineering that can profoundly change the way we design and interact with living systems.

What advice would you give to students that are interested in pursuing a similar career in research to yours?
My most important advice is to follow your curiosity. If you spend your time on things that deeply excite and fascinate you, you will be able to develop ideas and visions that are profoundly new and challenge the status quo. Also, excitement leads to motivation and ultimately stimulates high effort, all of which I believe are important ingredients for success in science. Moreover, you should find a great mentor who inspires you and supports you on the path you want to take. 
And finally: Trust your own judgment. It is certainly helpful to get advice and guidance by mentors and experts. But at the end of the day, the really exciting science often happens when everyone around you says they don't think it can work.