Project description
Inter-organelle dynamics in neuronal plasticity
The endoplasmic reticulum (ER) is a dynamic cellular structure with multiple functions, such as calcium storage, protein synthesis and lipid metabolism. The interplay of the ER with mitochondria is central in neurons for synaptic plasticity, but the underlying mechanism remains unknown. Funded by the Marie Skłodowska-Curie Actions programme, the SynERMCSs project aims to delineate the contribution of organelle dynamics in synaptic plasticity. Researchers will use super-resolution microscopy to study ER-mitochondria contact sites in live neurons. Results will provide unprecedented mechanistic knowledge into the role of ER in synaptic plasticity and neuronal physiology. Given that the communication between the ER and mitochondria is perturbed in neurodegenerative disorders, the project has clinical projections.
Objective
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.
Fields of science
- 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
Funding Scheme
MSCA-PF - MSCA-PFCoordinator
100 44 Stockholm
Sweden