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Protein synthesis is one of the most crucial steps in controlling gene expression. The speed at which a ribosome reads the mRNA transcript is not constant, but varies depending on the transcript and the encoded protein. This variation in ribosome speed is necessary for certain proteins to fold correctly. This has important implications for neurodegenerative diseases, which are characterised by the accumulation of misfolded and aggregated proteins. While we have a basic understanding of protein synthesis, we know little about the mechanisms that control ribosome speed in healthy and diseased neurons.

In this CORE project funded by the FNR, we will elucidate these mechanisms in neurons from patients with Parkinson’s disease (PD) and from healthy individuals. To this end, we will integrate ribosome interactomics, translatomics, and nascent proteomics data in order to shed light on co-translational protein misfolding in human dopaminergic PD ne...