Objective One of the major challenges in bacterial infectious disease relates to infections taking place in the bloodstream (septicemia). Despite availability of antibiotics these types of infections lead to extremely severe conditions such as septic shock or meningitis requiring a better understanding of mechanisms of disease. The common denominator of these conditions is the interaction of pathogens with the blood vessels and the subsequent alteration of the vessels biological properties. The aim of this project is to understand how such pathogens cause these dramatic alterations. This raises both biomedical and basic scientific questions that will be addressed in this project. How can these bacteria survive and multiply in the bloodstream? How do they interact with the endothelium? How do they affect vessel integrity and homeostasis? How can bacteria exit the vessel lumen to access the cerebrospinal fluid? Neisseria meningitidis is used as an experimental model in this project because it is a stereotypical example of septicemia and meningitis causing pathogen and because of the availability of experimental tools for its genetic manipulation. A central hypothesis of the project is that the ability of this bacterium to bind to endothelium and proliferate in aggregates inside the microvasculature, a process we refer to as vascular colonization, is central to the disease process. Our experimental approach is to generate innovative tools to reproduce the specific environment encountered by the bacteria in the bloodstream: blood flow generated shear stress, the specific geometry of the microcirculation, the human endothelium and its tissue environment. To meet these challenges we are using a multidisciplinary approach exploiting recent findings from the fields of physics, chemistry, microbiology, vascular biology and immunology. With this work we hope to unravel important pathophysiological mechanisms with implication for the management and treatment of sepsis and meningitis. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health scienceshealth sciencesinfectious diseasesmedical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE EU contribution € 1 500 000,00 Address RUE DE TOLBIAC 101 75654 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Guillaume, Marc, Luc Dumenil (Dr.) Administrative Contact Célestine Gomis (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France EU contribution € 1 500 000,00 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Guillaume, Marc, Luc Dumenil (Dr.) Administrative Contact Célestine Gomis (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
