Obiettivo 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. Campo scientifico natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesbiophysicsnatural sciencesphysical sciencesopticsspectroscopy Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Invito a presentare proposte FP7-PEOPLE-2013-CIG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-CIG - Support for training and career development of researcher (CIG) Coordinatore UNITED KINGDOM RESEARCH AND INNOVATION Contributo UE Nessun dato Indirizzo POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon Regno Unito Mostra sulla mappa Regione South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Tipo di attività Research Organisations Contatto amministrativo Gillian Carr (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Partecipanti (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto SCIENCE AND TECHNOLOGY FACILITIES COUNCIL Partecipazione conclusa Regno Unito Contributo UE Nessun dato Indirizzo Polaris House North Star Avenue SN2 1SZ SWINDON Mostra sulla mappa Tipo di attività Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contatto amministrativo Gillian Carr (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Partecipazione conclusa Regno Unito Contributo UE € 100 000,00 Indirizzo WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Mostra sulla mappa Regione South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Stephen Conway (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato