Stimulus- and time-dependent protein dynamics in autophagy analyzed by quantitative mass spectrometry
Description: Macroautophagy, hereafter referred to as autophagy, is a cellular recycling pathway. We investigate molecular mechanisms regulating, or regulated by autophagy with the help of quantitative mass spectrometry (MS)-based proteomics. Next to the ubiquitin/proteasome system, the autophagosomal/lysosomal system is responsible for the majority of cellular proteolysis. Autophagy is a basic cellular degradation pathway but also a cytoprotective stress-response. Its dysregulation is involved in numerous human diseases, such as neurodegenerative disorders and cancer. We are interested in regulatory protein-protein interactions, especially in underlying posttranslational protein modifications in stress-induced autophagy. For this, we follow a two-tiered strategy: (i) we investigate proteins known to be involved in autophagy regulation, and (ii) perform MS-based proteomics screens for the identification of new proteins being critical for stress-induced autophagy.Our main model system are human cell lines and primary cells. We are specifically interested in kinases regulating autophagy, e.g. Unc-51-like kinase 1 (ULK1) and MTORC1. MTORC1 is a master regulator of cellular homeostasis and negatively regulated autophagy by phosphorylating ULK1. Next to phosphorylation-based signaling, we study ubiquitination-based signaling and its role in autophagosomal cargo selection. In parallel, we perform unbiased approaches studying protein-protein interactions in autophagy inducing conditions to identify new autophagy regulatory proteins. By combining unbiased screening approaches with targeted MS analyses and development of new MS-based methods, we aim to characterize new molecular mechanisms regulating autophagy and being important for human health.
Amount: CHF 714,000
Funding type: research
Funder scheme: Project funding
Start date: 2019-04-01
End date: 2023-03-31
Investigator: Dengjel, Joern
Institution: University of Fribourg – FR
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 15
Funder award ID: 184781
OpenAlex ID: G4376162972