Obiettivo The blood-brain barrier controls the composition of extracellular fluid in the central nervous system and buffers against changes in the systemic circulation. The blood-brain barrier thus protects the nervous system against changes in the environment, and defects in the barrier contribute to many human disorders, including brain edema, auto-immunity and certain cases of obesity (defective leptin transport). The cells responsible for the establishment of the barrier are the brain capillary endothelial cells. Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Two different classes of integral membrane proteins constitute the tight junction strands, occludin and members of the cl audin protein family. The molecular basis for selective permeability regulation by these proteins is however only poorly understood. Our studies will be directed towards the establishment and characterisation of an in vitro BBB model suitable for further e lucidation of molecular tight junction function. We will establish a murine BBB in vitro and address the impact of vascular locality on paracellular blood-brain barrier permeability by the preparation of brain capillary endothelial cells from anatomically distinct brain areas. Moreover, since the nature of molecular interaction between the tight junction proteins occludin and the claudins is still poorly understood, biochemical and biophysical studies will address the role of molecular interactions between these proteins in the regulation of paracellular permeabiliy, with a special emphasis on their role in anchorage to the cytoskeleton. We further propose to analyse the structural organisation of claudins within the tight junction strands, which are hypothe sized to constitute permeability pores mediating selective paracellular permeability across the tight junction barrier. In this context, we will focus on investigation # Campo scientifico natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health scienceshealth sciencesnutritionobesity Parole chiave Anatomy Biophysics Cytochemistry Molecular Biology Nanotechnology Neurophysiology Programma(i) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Argomento(i) MOBILITY-4.1 - Marie Curie European Reintegration Grants (ERG) Invito a presentare proposte FP6-2002-MOBILITY-11 Vedi altri progetti per questo bando Meccanismo di finanziamento ERG - Marie Curie actions-European Re-integration Grants Coordinatore BAYERISCHE JULIUS-MAXIMILIANS UNIVERSITAET WUERZBURG Contributo UE Nessun dato Indirizzo Sanderring 2 WUERZBURG Germania Mostra sulla mappa Costo totale Nessun dato
