Our lab studies protein folding challenges and their role in aging and pathologies. A focus is on amyloid proteins whose aggregation is associated with late age of onset neurodegenerative diseases. We study the folding landscape of the amyloid proteins mutant Huntingtin, Abeta and tau in vitro and in vivo in the nematode C. elegans. We have identified specific chaperones that can suppress e.g. Huntingtin aggregation and reverse the aggregation by disaggregating Huntingtin fibrils. Using C. elegans models, we could show that the aggregation of amyloid proteins is associated with an early decline of neuronal activity and we observed that certain neurons are more vulnerable towards disease proteins than others and that this is specific for distinct amyloid proteins.
We aim to comprehensively understand how different nodes of the proteostasis network can be modulated to counteract the proteotoxicity of aggregating amyloid proteins. The proteostasis network is composed of molecular chaperones and proteolytic pathways including the proteasome and the autophagic flux. Our lab has developed several sensors to study the reciprocal relationship between molecular chaperones, the proteasome and the autophagic flux to cope with amyloid proteins as aging progresses. We could show that autophagy is activated when chaperone-mediated folding processes fail.