Ruprecht-Karls-Universität Heidelberg
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Bethune0118 - Scientist (f/m) / PhD position
Project no:
Bethune0118

Project leader:

Project supervisor:
Béthune, Julien
Application deadline:
31. Jul 2018
Start of PhD project:
1. Sep 2018

Project description:

Title:
RNA-binding proteins and neurodegeneration
Summary:
This project aims at characterizing how a novel RNA-binding protein (RBP) binds and represses the function of its mRNA targets and to address a possible link with the development of neurodegenerative disorders.

The protein GIGYF2 is a multifunctional protein with links to the IGF-I/EGF receptors signaling pathways and membrane trafficking. Recently, we have developed a novel proteomics technique termed split-BioID that allowed us identifying previously unknown interacting factors of the miRISC (miRNA-induced silencing complex). With this assay, we have uncovered GIGYF2 as a novel RBP that on the one hand modulates the miRNA-mediated gene silencing pathway and, on the other hand, can directly bind and repress its own mRNA targets in a GIGYF2-mediated silencing mechanism.

Interestingly GIGYF2 has been linked to the development of Parkinson’s disease and depletion of GIGYF2 in mice leads to motor dysfunction and neurodegeneration. However, the molecular basis for this phenotype is still elusive and may well be linked to the RNA-binding activity of GIGYF2.

To understand how GIGYF2 exert its mRNA silencing function and to explore if this activity is related to the development of neurodegenerative disorders, the project aims at comprehensively identifying the mRNAs that associate with GIGYF2 with which outcome on their stability and translation efficiency on a transcriptome-wide level.
References:
Amaya Ramirez, C.C., Hubbe, P., Mandel, N., and Béthune, J. (2018). 4EHP-independent repression of endogenous mRNAs by the RNA-binding protein GIGYF2. Nucleic Acids Res.

Schopp, I.M., and Béthune, J. (2018). Split-BioID - Proteomic Analysis of Context-specific Protein Complexes in Their Native Cellular Environment. J Vis Exp.

Schopp, I.M., Amaya Ramirez, C.C., Debeljak, J., Kreibich, E., Skribbe, M., Wild, K., and Béthune, J. (2017). Split-BioID a conditional proteomics approach to monitor the composition of spatiotemporally defined protein complexes. Nature Commun 8, 15690.

Giovannone, B., Tsiaras, W.G., de la Monte, S., Klysik, J., Lautier, C., Karashchuk, G., Goldwurm, S., and Smith, R.J. (2009). GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling. Hum Mol Genet 18, 4629-4639.
Methods that will be used:
- BioID/split-BioID
- RNAseq
- iCLIP
- Ribo-seq
Cooperation partners:
Personal qualifications:
We are looking for outstanding students interested in RNA biology and holding a Master degree in Biochemistry, Molecular Cell Biology, or comparable topics. The successful candidate will have a strong level of motivation, the ability to work independently within a small international team, very good knowledge of the English language (no German proficiency is required) and good computer skills. Previous experience with high-throughput techniques such as RNAseq, iCLIP or ribo-seq is a plus but not mandatory.
Keywords:
RNA-binding proteins, translation control, neurodegeneration