Structure and Function of Proteins

Structural biologists aim at deriving an understanding of the molecular basis of biological phenomena by obtaining images of the involved biomacromolecules at atomic resolution. We use protein crystallography to investigate proteins that play a role in infectious disease, e.g. by controlling the production of toxic molecules or by acting as toxins themselves. Our research in structural biology is complemented by biochemical and biophysical methods, and we also employ all these technologies to aid drug discovery projects at the HZI. 

Leader

We study proteins from microbial pathogens to unravel their role in infectious disease and to understand the details of how they work, thereby providing a basis for structure-guided 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 large amounts of 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.

Fig. 1: Phenazine biochemistry in Pseudomonas aeruginosa

Other important research activities investigate proteins from bacterial pathogens that cause life-threatening infections in the developed countries, such as Clostridium difficile or Staphylococcus aureus. 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. 

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  • Doppelt aktiviert besser

    Bakterien ist jedes Mittel recht, um einen Organismus zu infizieren. Sie dringen in Zellen ein, wandern durch den Körper, täuschen das Immunsystem oder missbrauchen Abläufe der Wirtszelle für ihre Zwecke. Jedes Bakterium hat dabei seine eigene Methode. Welche Mechanismen Listeria-Bakterien nutzen, haben jetzt Strukturbiologen des Helmholtz-Zentrums für Infektionsforschung (HZI) in Braunschweig herausgefunden. Der Trick der Erreger: Sie binden mit zwei Invasionsproteinen an einen Rezeptor auf menschlichen Zellen und lassen sich in die Zelle einschleusen. Diese Eintrittskarte ist eigentlich für Faktoren reserviert, die das Zellwachstum und die Wundheilung steuern. Sehen Sie, wie Professor Dirk Heinz und seine Arbeitsgruppe den Bakterien auf die Spur gekommen sind…
    Länge 06:15

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