Invitée direction: Dorothee Dormann, University of Mainz, Germany – “Molecular mechanisms controlling aberrant phase transitions in neurodegenerative diseases”

Résumé

Our research is focused on the molecular mechanisms that underlie the pathological redistribution and aggregation of RNA-binding proteins (RBPs) in neurodegenerative diseases, in particular ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia). We are especially interested in the RBPs TDP-43 and FUS, which are genetically linked to ALS and FTD and accumulate in aberrant cytoplasmic aggregates in the brains of ALS and FTD patients. Our previous work has shown that RBP mislocalization and aggregation is driven by defects in 1) nuclear import, 2) aberrant liquid liquid phase separation and 3) post-translational modifications of disease-linked RBPs. The talk will focus on recently discovered mechanisms that regulate phase separation and aberrant phase transitions of disease-linked RBPs, including nuclear import receptors (importins) and post-translational modifications.