Brandstetter
Image: © Luigi Caputo

The research of our team focuses on proteolytic enzymes, their cofactors, substrates and inhibitors. Proteolytic enzymes are master switchers in health and disease. By their highly specific recognition and modification of protein substrates, proteases serve as signaling and decision matrices. Of particular interest to us are proteolytic actions in the field of immunology/allergy, blood coagulation, and cancer.

We employ a broad spectrum of biochemical, biophysical and computational techniques to characterize the molecular function of important target proteins. Most importantly, we use x-ray crystallography to determine the three-dimensional architecture of the molecular targets. The structural information guides us to rationalize and experimentally test hypotheses about possible molecular mechanisms of action as well as their significance in the molecular, cellular and systemic context.

Questions of immunological interest are linked to the cellular pass control which is implemented via antigen processing and presentation. Each cell has to identify itself towards the immune system by presenting intracellular peptides at the cell surface. Despite its enormous efficiency, some harmful cells escape the screening (pass control) of the immune system, e.g., by presenting unsuspicious peptides only. On the other side, allergens, which are per se harmless proteins, can trigger excessive immune reactions. We investigate the complex protease machines involved in antigen processing. A detailed understanding promises treatment options against immunological and infectious diseases, and also tumors.

The (innate) immune system is multiply linked to the blood coagulation system which primarily serves to stop life-threatening bleeding without causing fatal vessel occlusions (thrombosis). For this purpose nature employs a molecular proofreading principle that requires simultaneous and concerted molecular actions. We investigate disharmonies in these molecular orchestra that lead to bleeding disorders such as hemophilia.

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