Project 466717

Our model is the absorption system of nickel ions in Helicobacter pylori,one of the most performant human pathogenic agents causing light to severe gastric pathologies. These bacteria are considered a major cause of gastric cancers and lymphomas of MALT type. My project aims to characterize the molecular mechanisms of the transport of organometallic molecules across the membrane of H. pylori using structural biology and biochemistry approaches. The objective of the project is to accelerate the research about the medically pertinent and less studied proteins by elucidating their structures and their functional mechanisms. This will be done in order to guide the development of new anti-pylori molecules with better diffusion and assimilation properties. In order to achieve this, my Masters project objectives will be to develop the production tools for the 4 nickel transporters NiuB, NiuDE, FecA3 and Frpb4 implied in the transport of bismuth salts. I will be using a heterologous expression system (Escherichia coli) for the production of recombinant proteins. The genes have already been synthesized (codon optimization) and inserted in compatible pET vectors. Easing the purification by affinity chromatography via the presence of the histidine tag. Once the production and purification method will be established, I will start the crystallization trials in order to elucidate the structure of these proteins in the presence and absence of the drugs. Ultimately, my transporter-ligand structural data will lay the experimental foundations that will facilitate the development of new therapeutic molecules