Obiettivo noMAGIC has the visionary goal of engineering genetically encoded ion channels, which can be remotely controlled (gated) by stimuli that penetrate deep into human tissue without negative side effects. The control over ion channel activity by deep penetrating stimuli will revolutionize research in neurobiology and physiology as it paves the way for remote and genuine non-invasive control of cell activity in vivo. Synthetic channels, which can be gated by magnetic fields (MF), near infrared (NIR) radiation or ultrasound (US) will be engineered in the frame of noMAGIC by three complementary work packages (WP1-3). Design and engineering of the channels will be performed in WP1 by reiterated steps of rational and irrational design, high throughput screening and in vitro and in vivo functional testing. We have identified two sensor modules for MF and NIR radiation, respectively, which will be functionally connected to a channel pore for a remote control of gating. For the US-gated channel we will engineer a channel pore that is maximally responding to local changes in the lipid environment induced by US. Design and engineering of channels will be complemented by a computational approach (WP2), which analyses, from elastic network models, the mechanical connections in the channel pore and which extracts information on the forces, which are required to gate a channel by the three stimuli. The outcome of WP2 will provide general design rules for synthetic channels with implications much beyond the present project. WP3 also contributes to the engineering effort in WP1 by a spectrum of avant-garde spectroscopic methods, which resolve structural changes of the channel proteins under the influence of remote stimuli. These structural insights will greatly advance our understanding of structure/function correlates in composite ion channels and it will inspire the design and engineering of channels, which respond to remote stimuli. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesphysical sciencesopticsmicroscopyconfocal microscopynatural sciencesphysical sciencesopticsfibre opticsnatural sciencesphysical sciencesacousticsultrasound Parole chiave ion channels gating optogenetics K+ channels Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-ADG-2015 - ERC Advanced Grant Invito a presentare proposte ERC-2015-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante UNIVERSITA DEGLI STUDI DI MILANO Contribution nette de l'UE € 1 825 344,00 Indirizzo Via Festa Del Perdono 7 20122 Milano Italia Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 825 344,00 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSITA DEGLI STUDI DI MILANO Italia Contribution nette de l'UE € 1 825 344,00 Indirizzo Via Festa Del Perdono 7 20122 Milano Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 825 344,00 TECHNISCHE UNIVERSITAT DARMSTADT Germania Contribution nette de l'UE € 583 865,00 Indirizzo KAROLINENPLATZ 5 64289 Darmstadt Mostra sulla mappa Regione Hessen Darmstadt Darmstadt, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 583 865,00
