Objectif Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing calcium buffering at sites of calcium entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Moreover mutations in proteins regulating mitochondrial trafficking compromise neuronal development and the formation, function and plasticity of synapses, and defective mitochondrial trafficking is increasingly implicated in neurological diseases. Understanding the molecular mechanisms that allow neurons to tailor the distribution of mitochondria to changes in neuronal activity therefore has important implications for our understanding of neuronal function and communication. This proposal will study the mechanisms that control the trafficking of the energy providing mitochondria within neurons, and how this relates to neuronal connectivity and plasticity. Using imaging, electrophysiological, molecular and cell biological techniques, combined with viral transduction and mouse transgenic approaches we will determine the molecular mechanisms underlying the activity-dependent subcellular positioning of mitochondria in neurons. We will examine how the mitochondrial Ca2+-sensing GTPases Miro1 and Miro2 act to regulate mitochondrial movement, distribution and function and how this contributes to neuronal development, synaptogenesis and synaptic plasticity. A key goal will be to determine if different roles exist for constitutive versus activity-dependent control of mitochondrial transport by Miro1 and Miro2 in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial localisation in neurons and the role that activity-dependent mitochondrial trafficking plays in regulating neuronal development, morphogenesis, connectivity and function. Champ scientifique natural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation 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) Thème(s) ERC-SG-LS5 - ERC Starting Grant - Neurosciences and neural disorders Appel à propositions ERC-2011-StG_20101109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITY COLLEGE LONDON Contribution de l’UE € 1 997 567,00 Adresse GOWER STREET WC1E 6BT London Royaume-Uni Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Higher or Secondary Education Establishments Contact administratif Giles Machell (Mr.) Chercheur principal Josef Kittler (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITY COLLEGE LONDON Royaume-Uni Contribution de l’UE € 1 997 567,00 Adresse GOWER STREET WC1E 6BT London Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Higher or Secondary Education Establishments Contact administratif Giles Machell (Mr.) Chercheur principal Josef Kittler (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
