Objectif
Transportation of proteins and lipids between membrane-enclosed organelles by vesicle formation is a fundamental task in eukaryote cells. The least understood protein complex involved in membrane remodelling for vesiculation, but with a wide range of medical implications, is the retromer complex.
The objective of this proposal is:
First, to identify the mechanistic principles of membrane bending and scission by retromer, and second to characterize temporal and morphological aspects of retromer and cargo molecules (Shiga toxin (STx) and Alzheimer’s amyloid-beta-cleaving enzyme (BACE)).
I will exploit two approaches:
First, in vitro reconstitution of the retromer complex using giant unilamellar vesicles to deploy biophysical methods.
Second, I will provide a molecular choreography and anatomy of retrograde transport of STx, BACE and retromer by implementing a new imaging technique, structured-illumination microscopy combined with single particle tracking.
The proposed interdisciplinary research will break new ground for membrane mechanics and trafficking of disease related cargo molecules.
Champ scientifique
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesbasic medicineanatomy and morphology
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Appel à propositions
FP7-PEOPLE-2010-RG
Voir d’autres projets de cet appel
Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
75231 Paris
France