For the effective combat of infectious diseases, they must be understood as precisely as possible - right down to the molecular level. "We want to know how certain proteins interact with other molecules in the context of infections. And we want to learn how these proteins look like at the atomic level and how they move, in other words, how their dynamic is constituted," says Ute Hellmich, new professor of Biostructural Interactions at the Faculty of Chemistry and Earth Sciences at the Friedrich Schiller University Jena, based within the Cluster of Excellence Balance of the Microverse.

When unexpected measurement data turn into new discoveries

Surprising things can be discovered when researching the interactions of biomolecules, for example of so-called trypanosomes: "These are single-celled parasites that can cause tropical diseases, such as African sleeping sickness. In order to survive, these parasites need a certain enzyme. However, there are molecules that inhibit this enzyme, i.e. act as inhibitors. For one of these inhibitors, we wanted to find out exactly how this works." When she and her team examined the chemical complex that the inhibitor forms with the enzyme, they encountered unexpected measurement signals. "At first, we thought we were observing artifacts," the biochemist recalls. "However, we soon realized that the enzyme-inhibitor complex combines with another identical complex from the environment - it dimerizes. The inhibitor molecule functions like a glue in this process," Prof. Hellmich explains. Thus, her research group discovered one of the smallest known molecules that exhibit this behavior. "These so-called dimerizers are of great pharmaceutical importance. They can be used, for example, to control signaling pathways in the cell," Prof. Hellmich classifies this unexpected discovery.

One important method she uses to study the interactions of enzymes and other biomolecules is nuclear magnetic resonance spectroscopy. "This method is excellent for studying atomic details of complex biological building blocks. In addition, we can also study the dynamics of our samples and describe their function," the scientist explains. "However, we don't want to obsessively commit to a single method, but rather use all possibilities to answer our respective questions."

This requires a lot of collaboration between experts from different disciplines. "Of course, proteins come from Biochemistry. But in Synthetic Chemistry, the inhibitor molecules are made and modified. Biophysical chemistry provides the investigation methods. And Theoretical Chemistry helps us to derive new and improved structures from the information obtained," Prof. Hellmich sums up.

Researching neglected tropical diseases

For Prof. Ute Hellmich, however, interdisciplinarity does not end with the natural sciences. "One of our central research topics is the so-called neglected tropical diseases. Socio-political factors also play a crucial role, such as livestock management, settlement, climate change, but also history, for example, when it comes to understanding whether and how drugs or vaccines are developed and for whom they are actually available. We see the effects of such inequalities today as well, such as in the global distribution of COVID-19 vaccines."

The path between biochemistry and the humanities has recently been entered by a doctoral student in her group. "This path is very unusual for a natural scientist, and I'm excited to see what comes out of this work, which is also new for us. We have a responsibility as researchers to look right and left of the track and to think outside our box about our topics."

"A luxury to work at such a broad-based university"

After earning her PhD at the Goethe University Frankfurt/Main in 2010, the biochemist conducted research for several years at the Harvard University in Cambridge, Massachusetts. From 2015 to 2020, she was Junior Professor of Membrane Biochemistry at the Johannes Gutenberg University Mainz, where she successfully completed her tenure track in 2020. Since this year, Prof. Ute Hellmich and her group are in Jena as part of the Microverse Cluster.

For the biochemist, the environment at the Friedrich Schiller University is ideal. "It is a luxury to work at such a broad-based university. I hope that many new encounters will take place here." That these are already taking place is shown by the fact that, while she is still setting up her labs in Jena, a bachelor's student, a master's student and a doctoral student from Jena are already researching their theses.

Text by Roman Witt based on the German press releases by Marco Körner (University of Jena)