"The main goal of this proposal is to determine how the deadly bacterial pathogen, Neisseria meningitidis (NM), crosses the blood-tissue barriers and invades the brain and other vital organs. The main hypothesis behind this project is that NM, by interacting with the vascular endothelial cells with its pili, induces a signal that opens cell-to-cell junctions and allows the bacteria to penetrate the natural barriers using the paracellular route rather than the transcellular one as currently accepted. The methodology to be applied involves multidisciplinary approach with advanced imaging techniques, mass spectroscopy, basic cell biology and molecular genetics, and is aimed to take advantage of complementary expertise of involved research partners to solve this burning clinical issue. Understanding the mechanism by which a bacterial pathogen invades the brain and other organs will have consequences beyond the field of medical bacteriology, and will allow insights into regulation of cell polarity. Information gained from this study will be aid in the design of vehicles that mimick signals generated by N.meningitidis, and thus contribute to the design of new systems for the delivery of drugs beyond the blood brain barrier."