Structure and Function of Proteins

We study proteins from microbial pathogens to unravel their role in infectious disease and to understand details of how they work, thereby providing a basis for structure-guided rational development of novel anti-infectives. Our research projects mainly investigate protein/small molecule interactions in pathogenic bacteria, for example in the biosynthesis and regulation of toxic molecules or towards the development of inhibitors of these processes.

The most important model organism in our group is the bacterium Pseudomonas aeruginosa. This infamous “hospital bug” is not only responsible for disease in hospitals but also in cystic fibrosis, where it establishes chronic lung infections in nearly all patients and leads to early mortality. P. aeruginosa produces numerous virulence factors such as e.g. phenazines, a class of redox-active toxins that cause tissue damage to the patient but may also act as respiratory molecules that P. aeruginosa needs to survive in biofilms. In addition to phenazine biosynthesis, where we have derived a detailed understanding of the participating enzymes, we also investigate its regulation through the Pseudomonas Quinolone Signal PQS, a unique system that may particularly well-suited for being targeted by new pharmaceuticals such as those developed in collaboration with other researchers at the HZI. Further, we study potential phenazine resistance factors in P. aeruginosa, since inhibiting these proteins may lead to specific self-poisoning of the bacterium.

Other important research activities investigate proteins from bacterial pathogens that cause life-threatening infections in the developed countries, such as Clostridium difficile, Staphylococcus aureus or Legionella pneumophila. Here, we investigate key metabolic processes and toxic proteins that are essential for the survival or pathogenicity of these organisms. We are also involved in collaborative projects with other groups at the HZI and at neighboring research institutions, where we contribute our expertise in recombinant protein production, structural biology and biochemical characterization.