Doctoral researcher on ribosome speed control in neurodegeneration

University of Luxembourg, Luxembourg

Updated: 2 days ago
Deadline: ;

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 neurons. We will then combine these findings with genetic patient information to identify critical mutations in translation regulators that may affect the rate of protein synthesis.

This project will establish the concept of translation dysregulation as an important new area of PD pathogenesis for developing new translation-based drugs.

This project focuses on transcriptomics and proteomics experiments, as well as interactomics and kinetic translatomics of translating ribosomes and their genetic manipulation in dopaminergic neurons from various PD models. The aim is to use these findings to identify translationally aberrant protein products that have a high propensity to aggregate. This will form the basis of testing various translation modifiers to restore translational dysregulation in these cells. The candidate will be responsible for differentiating neural stem or progenitor cells into dopaminergic neurons and performing all omics experiments. The person will also be responsible for validating the findings, testing translation modifiers and assisting with the analysis.


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