Under the framework of the ERC Starting Grant project, LEXSYN (10.3030/101161748), we investigate these lysosomes. Key questions include: How is this process regulated in the intact brain? What are the consequences of lysosomal fusion with the plasma membrane? Can glial cells sense lysosomal fusion? Can we manipulate this process to prevent protein aggregation associated with age-related neurodegenerative diseases like Huntington's disease, Alzheimer's disease, and Frontotemporal dementia?
To explore these questions, we employ molecular biology techniques and advanced fluorescence microscopy, ranging from super-resolution STED and STORM techniques, TIRF live-imaging, to 2-photon in vivo imaging. Utilizing genetically encoded probes and optogenetic tools to manipulate the acidification and positioning of neuronal organelles, we investigate the relationship between these organelles and synaptic function.