Description du projet
Dynamique inter-organites dans la plasticité neuronale
Le réticulum endoplasmique (RE) est une structure cellulaire dynamique qui remplit une pluralité de fonctions, notamment le stockage du calcium, la synthèse des protéines et le métabolisme des lipides. L’interaction entre le RE et les mitochondries est essentielle dans les neurones afin d’assurer la plasticité synaptique, mais le mécanisme sous-jacent demeure inconnu. Financé par le programme Actions Marie Skłodowska-Curie, le projet SynERMCSs vise à déterminer la contribution de la dynamique des organites à la plasticité synaptique. Les chercheurs auront recours à la microscopie à super-résolution pour étudier les sites de contact RE-mitochondries dans des neurones vivants. Les résultats généreront des connaissances mécanistes inédites sur le rôle du RE dans la plasticité synaptique et la physiologie des neurones. Les maladies neurodégénératives étant caractérisées par une perturbation de la communication entre le RE et les mitochondries, le projet présente des applications cliniques.
Objectif
The endoplasmic reticulum (ER) can rapidly reorganize its functional domains and inter-organelle communication sites in response to cellular demands. ER-mitochondria communication is essential for normal cell physiology, as it conveys lipid exchange, mitochondrial calcium uptake, among other vital processes for mitochondrial function. In neurons, activity-mediated dynamics of ER and mitochondria are required for synaptic responsiveness to induction of synaptic plasticity and stimulating neuronal activity increases the number of ER-mitochondria contact sites (ERMCSs). Whilst system modelling predicts that ERMCSs control the postsynaptic energy landscape, the actual contribution of synaptic and perisynaptic inter-organelle dynamics to synaptic plasticity is still quite unknown.
The small and compact structure of dendrites constrains the visualization of local ER-mitochondria contact site dynamics, being the application of nanoscopy techniques fundamental to follow these processes upon induction of synaptic plasticity. The use of cutting-edge super-resolution microscopy in this project will provide unprecedented spatiotemporal resolution to the study of activity-mediated ER and mitochondria dynamics and inter-organelle contacts heterogeneity in live neurons. Likewise, it will clarify the contribution of ERMCSs to sustain normal dendritic physiology as well as the intricate system triggering and upholding synaptic plasticity. Dysfunction of the ERMCSs has been reported in various neurodegenerative disorders due to mutation in proteins promoting and supporting ER-mitochondria communication. Neurodegenerative disorders are responsible for a great burden in disease, as dementias alone affect over 7 million people in Europe and this figure is expected to increase dramatically with aging of the population.
Champ scientifique
- natural sciencesbiological sciencesneurobiology
- natural scienceschemical sciencesinorganic chemistryalkaline earth metals
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicinephysiology
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
MSCA-PF - MSCA-PFCoordinateur
100 44 Stockholm
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