what we do
Aggregation-associated, neurodegenerative diseases (NDs) pose a major societal and economic burden that drastically affects the lives of both patients and family caretakers. A unifying theme that connects these NDs is their strong association with an aging-dependent, progressive failure of cellular maintenance mechanisms that control pathological protein misfolding and aggregation.
In our lab, we are interested in aspects of pathological protein aggregation as well as the post-translational regulation of the cellular proteostasis machinery in health and disease. Current projects include:
Post-translational regulation of chaperone activity: Eukaryotic cells have evolved elaborate mechanisms that assist protein translation, folding and proteosomal degradation, a process termed proteostasis. Heat shock proteins (HSPs) are key members of the proteostasis machinery, but beyond transcription, the intracellular regulation of HSPs remains poorly understood. Given their overall abundance and central role in protein folding, the concept of reversible HSP regulation by post-translational protein modifications (PTMs) has emerged as a new paradigm.
We aim to investigate how PTMs, such as phosphorylation or AMPylation, control HSP function in health and disease. We use complementary in vitro and in vivo models to study how post-translational HSP modifications alter protein aggregation dynamics. Caenorhabditis elegans models are used to test novel concepts of HSP regulation and to investigate how HSPs affect protein aggregation. Our research will yield new mechanistic insights into the relationship between PTMs and protein aggregation.
The molecular basis of CAG/polyQ repeat aggregation: We are interested in investigating neurodegenerative polyQ repeat disorders such as Huntington’s disease and sporadic cerebellar ataxias. We aim to decipher how, when and why polyQ repeat proteins start to aggregate and intoxify cells.
For both projects, emerging hypotheses will be validated using human tissue culture (TC) models as well as ex vivo human brain tissue from healthy donors, and ND patients. Our research will provide insights into the molecular basis of proteostasis and may identify new routes to ameliorate the pathology of aging-associated neuropathologies.