A structural biology approach to the study of virulence factors of the carcinogenic bacterium Helicobacter pylori.

Helicobacter pylori persistently colonize the epithelium of the stomach in roughly half of the world’s population. It is a causative agent of gastric and duodenal ulcers, mucosa- associated B-cell lymphoma and gastric adenocarcinoma. Although it is a definitive carcinogen, there is no effective vaccine against this bacterium. Standard H. pylori eradication therapy now fails in up to 30%-40% of patients, mainly due to an increase in clarithromycin resistance. There is a clear demand for new strategies to fight H. pylori infections, strategies that involve new or unconventional targets for drug design. A key to success with this lies in strong basic knowledge of the molecular basis of bacterial virulence and survival. Our laboratory focuses on the mechanisms of acid acclimation, damage to gastric epithelial cells and motility and chemotaxis. We use in vitro molecular biophysics and crystallography techniques to investigate structure and dynamics of biomolecules and formulate hypotheses about molecular mechanisms which we then test in vivo using genetics, enzymology and cell biology methods. Applications are welcome from students with a strong interest in the biology of H. pylori, protein biochemistry or structural biology/crystallography.