The laboratory for Membrane Trafficking (Prof. Wim Annaert) studies the cellular biology of Alzheimer’s disease (AD) and aims to understand how intracellular transport regulation contributes to intramembrane proteolysis of APP and the production of neurotoxic Aβ peptides.
Recent work from the lab (Sannerud et al., Cell, 2016) showed that PSEN2/γ-secretase generates the prominent pool of intracellular Aβ and familial AD-associated mutations strongly increase the accumulation of longer Aβ. Herein it was striking to find PSEN2 complexes organized in nanodomains on the limiting endosomal/lysosomal membrane.
This project will focus on exploring this nanodomain organization of PSEN/γ-secretase complexes in cell models including differentiating neurons using subdiffraction microscopy or nanoscopy. The laboratory has in-house PALM/STORM and SIM microscopy and closely collaborates with spectroscopists Prof. Johan Hofkens and Prof. Hideaki Mizuno in the Science and Technology group at KU Leuven to improve nanoscopy modalities and explore novel fluorescent probes. The project is focused on nanodomain analysis and bridges with basic neuro- and lysosomal biology in the context of Alzheimer’s disease pathogenesis.