Gerd Katzenmeier, Ph.D.
|Ph.D. (Biochemistry), Technical University of Munich, 1991
Field of Research: Structural and functional properties of pore-forming microbial toxins
The Laboratory of Molecular Microbiology is integrated in the Bacterial Protein Toxin Research Cluster which aims at elucidating structure-function relationships within prokaryotic protein toxins by using a broad array of molecular biological, biochemical and biophysical methods. Specifically, our research is directed towards enhancing our understanding of the mechanism of action of the vacuolating cytotoxin VacA from Helicobacter pylori. Helicobacter pylori is associated with severe and chronic diseases of the stomach and duodenum such as gastritis, peptic ulcer, non-cardial adenocarcinoma and gastric lymphoma. The vacuoloating cytotoxin VacA is one of the major virulence factors possessing unique properties which are unrelated to other pore-forming bacterial toxins. Despite the accumulation of substantial data over the past years, several aspects of VacA-related activity have been characterized only to a limited extend. These include i) the precise molecular mechanism and structural determinants of membrane insertion and pore formation; ii) the structural requirements for oligomerization, receptor-binding and internalization and iii) the structural basis for disparate activities of allelic variants contributing differently to pathogenicity and disease severity. The current investigations in our laboratory aim at i) the analysis of structural determinants for membrane insertion and channel formation including crystallographic studies on the pore-forming p33 domain, ii) the identification and characterization of cellular receptor(s) for VacA and the biochemical and biophysical investigation of molecular interactions between the VacA toxin and its receptor(s) and iii) a comparative analysis of sequences, structures and biological activities of VacA from Thai clinical isolates.