专题讨论口头报告张维伦范本.pptVIP

Helicobacter exploits integrin for type IV secretion and kinase activation 指導老師: Outline Introduction Hypothesis Specific Aims Aim1: Aim2: Results (experiment design and data) Summary Inspiration and future works Your comments for the paper H. Pylori and gastric cancer (Introduction) Cag pathogenicity island Encode oncoprotein – cagA Encode type IV secretion system Hypothesis Integrins are exploits by H. pylori for injection of cagA into gastric epithelial cells Specific Aims Integrin α5β1 is involved in type-IV secretion CagL is expressed on type-IV secretion pili CagL is essential for type-IV secretion CagL binds integrin α5β1 CagL activates FAK and Src tyrosine kinases Step 1. Integrin α5β1 is involved in type-IV secretion of CagA Co-localization of phosphorylated CagA with vinculin during H. pylori infection β1 is required for injection of CagA into target cells α5 is required for injection of CagA into target cells Co-localization of phosphorylated CagA (CagA-pY) with vinculin during H. pylori infection Study design Result Step 2. CagL is expressed on type-IV secretion pili CagL is the only gene product that contains RGD motif CagL is expressed on the surface of H. pylori CagL CagA signals are present at the tips of H. pylori’s pili Pilus formation is CagL- and RGD-dependent CagL is the only gene product that contains RGD motif Method Sequence analysis of cagPAI gene Step 3. CagL and its RGD motif are essential for type-IV secretion Study design Results Step 4: CagL binds integrin α5β1 in an RGD-dependent manner Study design Step 5: CagL activates FAK and Src tyrosine kinases CagL (wt) strain can activate FAK and Src, while CagL (RGA) can not Recombinant CagL (RGD) can activate FAK and Src, while CagL (RAD) can not Results Inspiration and future works Thinking process and study design CagL may be a novel vaccination target to decrease the bacterial virulence Regulation of cell surface integrin may be potential to prevent