Objectif The organization of the T-cell in its resting and activated state, specifically of plasma-membrane molecules involved in the triggering of the T-cell, is a long-standing and contentious research topic in molecular immunology. Understanding the molecular mechanisms involved at the nanoscale, i.e. at spatial scales below the resolution limit of conventional optical microscopy (< 200 nm) will find answers to still open questions, and offer new routes to immunotherapy. The proposed multidisciplinary project aims to bring close together super-resolution STED microscopy and membrane biophysics with molecular immunology. The proposed studies will follow a holistic approach and include the investigation of the functional associations of a multitude of molecules in T-cell triggering, ranging from the T-cell receptor and co-receptors, over other proteins such as kinases and phosphatases, to lipids and the cortical cytoskeleton. Using super-resolution STED and single-molecule microscopy (specifically STED and fluorescence correlation spectroscopy, STED-FCS) I will directly observe, determine, follow and evaluate nanoscale molecular interactions of these molecules from the resting state and early activation of the T-cell until the constitution of the immunological synapse. Besides a sophisticated design of the experimental conditions such as appropriate live-cell fluorescence labeling, biochemical treatments and choice of activating the T-cell, I will improve the STED-FCS technology towards multi-color observations allowing the determination of nanoscale dynamics and interactions of different specific molecules at the same time. With new molecular interactions highlighted, I will be able to better understand how T-cells sense antigen presenting cells and what molecular ramifications are involved during the constitution of the immunological synapse. Champ scientifique natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesbiophysicsnatural sciencesphysical sciencesopticsspectroscopy Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur UNITED KINGDOM RESEARCH AND INNOVATION Contribution de l’UE Aucune donnée Adresse POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon Royaume-Uni Voir sur la carte Région South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Type d’activité Research Organisations Contact administratif Gillian Carr (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire SCIENCE AND TECHNOLOGY FACILITIES COUNCIL Participation terminée Royaume-Uni Contribution de l’UE Aucune donnée Adresse Polaris House North Star Avenue SN2 1SZ SWINDON Voir sur la carte Type d’activité Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contact administratif Gillian Carr (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Participation terminée Royaume-Uni Contribution de l’UE € 100 000,00 Adresse WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Voir sur la carte Région South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Type d’activité Higher or Secondary Education Establishments Contact administratif Stephen Conway (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée