Dr. Tobias Madl

Proteins under the Hammer

Proteins are the building blocks of life. If something goes wrong during their production, diseases such as diabetes, cancer and neurodegenerative changes can be the result. Using state-of-the-art equipment, Tobias Madl and his ten-member team of the junior research group “Structural Biology of Signal Transduction” are searching for the molecular causes of such production errors. 

Tobias Madl untersucht Raumstrukturen von Eiweißen, die Signale zwischen Zellen übermitteln. Er will herausfinden, wie fehlerhafte Proteine (im Bild Transportin) zur Entstehung von Krankheiten führen; Quelle: HMGU

During his studies, Tobias Madl was also interested in physics, computer science and history. Whether in historical archives or in the chemistry lab – the main objective for the future chemist was to break new ground and to close knowledge gaps. “To have new things to discover and to thus benefit mankind, that’s what drives me forward,” he says, describing his motivation. For him it is important to have the freedom to look right and left. “That is not a waste of time, but rather serves a purpose.”

Madl‘s Team is based at the Institute of Structural Biology (STB) and the Bavarian NMR Center, which is run jointly by Technische Universität München and Helmholtz Zentrum München. The group maintains close cooperation on various levels. In collaboration with the Institute of Molecular Cancer Research at the University of Utrecht, the researchers explore how signal transductions are influenced by defective proteins and by the environment, e.g. oxidative stress, thus leading to the development of cancer. Together with the Ludwig-Maximilians-Universität München and the German Center for Neurodegenerative Diseases, the role of RNA-binding proteins is analyzed in the regulation of signal transduction. And finally, with partners from the University of Tübingen, the group checks whether the molecular and cell biological findings are confirmed in clinical studies. “These collaborations make it possible to bridge the gap between the disease and the molecular causes," says Madl, describing the synergy.

For the first step, the characterization of the proteins, the group in the Bavarian NMR Center has access to state-of-the-art NMR spectroscopy equipment. Using these devices, Madl analyzes the spatial structure and the interaction of the protein areas. To explain the highly complex method, the chemist illustrates it with a comparison: “We hit with a hammer on the atoms in the molecules and listen as they scream. From the data on the location and strength of the scream we can derive the spatial structures of the proteins and investigate interactions between the protein areas.”

To obtain information regarding the form of the biomolecules complementary to the NMR spectroscopic data, the team uses the SAXS system to measure the small angle X-ray scattering. Using a program Madl developed, these data are combined with the NMR data to obtain the structural and dynamic characteristics of the target protein. Step by step, the researchers are now beginning to study the individual elements in detail. Their aim is to find out which structures are responsible for the development of diseases and which could serve as potential drug targets.

To elucidate the interactions between proteins and other cell organelles, different methods must be combined. “I am therefore glad that at Helmholtz Zentrum München there is a great concentration of outstanding biological research. Here I can also study how environmental factors regulate proteins and whether they are responsible for dysregulations“, says Madl. In his opinion, scientific exchange with other research groups is essential to answer these challenging questions. Besides scientific expertise, the research group leader therefore places emphasis on social competence: “We are happy to measure ourselves against external competition. But within the team there is no place for this – we all are dependent on each other and benefit from each other.”