Deciphering the mechanisms for organellar crosstalk and repercussions on proteotoxicity in yeast models for neurodegeneration.

There is an urgent need for effective therapeutic strategies and tools for early diagnosis of proteinopathies like Alzheimer’s or Parkinson’s Disease. These diseases are characterized by a multi-factorial etiology, involving different cellular organelles. In this project, we will elucidate the mechanisms underlying organellar crosstalk with focus on interactions allowing for metabolic exchange between the vacuole/lysosome, mitochondria and endoplasmic reticulum. This insight will then be used to investigate how aggregation-prone disease proteins affect this crosstalk and, conversely, how the crosstalk mechanisms affect the cytotoxicity of these disease proteins. This will provide novel starting points for development of novel diagnostic tools and disease-modifying treatments.