Reference : FR550-MAGTOR-013
Workplace : PARIS 05
Date of publication : Wednesday, September 14, 2022
Type of Contract : FTC Scientist
Contract Period : 24 months
Expected date of employment : 1 January 2023
Proportion of work : Full time
Remuneration : Starting from 3106 EUR (gross salary per month), depending on experience
Desired level of education : PhD
Experience required : Indifferent
PI: Valérie Heurgué-Hamard (email@example.com)
Protein synthesis is a finely-tuned and tightly-controlled process ensuring normal cell growth and allowing cells to adapt throughout the cell cycle and in response to environmental cues. Post-transcriptional and post-translational modifications occur at high frequency in the ribosome (proteins, rRNA), tRNAs and translation factors, where they play a major role in the global regulation of protein synthesis. They can also play a role in the efficiency/accuracy of translation and in ribosome biogenesis with established consequences on cell cycle progression in eukaryotes.
Methylation is one of the most common modifications observed on proteins and RNAs. Remarkably, in yeast and humans, two thirds of known methyltransferases (MTases) are dedicated to the translation machinery. The involvement of these modifications in translation is perfectly illustrated by the unique yeast protein Trm112. Trm112 serves as an activating platform for four methyltransferases (MTases) involved in rRNA (Bud23), tRNA (Trm9 and Trm11) and translation termination factor (Mtq2) modification, ideally placing it at the interface between ribosome synthesis and function to potentially regulate both processes.
Trm112-MTase complexes are widely conserved in eukaryotes and archaea. Their human orthologues have been implicated in the development of cancer, neurodegenerative disorders and viral infections. New Trm112 partners were recently identified in mammalian cells and archaea. Using S. cerevisiae as a model organism, our lab has shown how Trm112 is involved in the synthesis of both ribosomal subunits via its interaction with Bud23 and Mtq2, but the mechanisms remain to be characterized in detail. The present post-doctoral project also aims to decipher the regulation and dynamics of the Trm112-MTase network during the cell cycle, and in response to various stimuli. It is anticipated that this two-tiered project will improve scientific recognition of the candidate through high standard publications.
We will use several complementary experimental approaches such as yeast genetics, molecular biology, physiological studies, biochemistry, immunoprecipitation followed by mass spectrometry and potentially structural biology if new complexes are validated.
Representative publications of the group on this theme
Lacoux, C., Wacheul, L., Saraf, K., Pythoud, N., Huvelle, E., Figaro, S., Graille, M., Carapito, S., Lafontaine, D.L.J & Heurgué-Hamard, V (2020) The catalytic activity of the translation termination factor methyltransferase Mtq2-Trm112 complex is required for large ribosomal subunit biogenesis. Nucleic Acids Res. 48, 12310-12325.
Létoquart, J..,Huvelle, E.., Wacheul, L.., Bourgeois, G., Zorbas, C., Graille, M., Heurgué-Hamard, V & Lafontaine D.L.J. (2014) Structural and functional studies of Bud23-Trm112 reveal 18S rRNA N7-G1575 methylation occurs on late 40S precursor ribosomes. Proc. Natl. Acad. Sci. 111, E5518-E5526
Figaro, S., Wacheul, L., Schillewaert, S., Graille, M., Huvelle, E., Mongeard, R., Zorbas, C., Lafontaine, D#., Heurgué-Hamard, V# (2012) Trm112 is required for Bud23-mediated methylation of the 18S rRNA at position G1575. Mol Cell Biol, 32, 2254-2267
Liger D, Mora L, Lazar N, Figaro S, Henri J, Scrima N, Buckingham RH, van Tilbeurgh H, Heurgué-Hamard V, Graille M. (2011) Mechanism of activation of methyltransferases involved in translation by the Trm112 « hub » protein. Nucleic Acids Res. 39, 6249-59.
Figaro, S., Scrima, N., Buckingham, R.H & Heurgué-Hamard, V. (2008) HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS letters, 582, 2352-2356.
- Biochemistry (protein, RNA purification and analysis, polysome analysis, western blots, immunoprecipitation experiments)
- Production and analysis of proteomic (mass spectrometry) data
- Enzymatic activity assays
- Molecular biology (cloning, plasmid mutagenesis, nucleic acid preparation, PCR)
- Genetics in the bacteria E. coli and yeast Saccharomyces cerevisiae (mutagenesis, transformations, tools for controlling gene expression)
- Knowledge of mRNA translation mechanisms, ribosome biogenesis, protein and RNA methylation
- Knowledge in regulation of gene expression in yeast
- Good knowledge in molecular biology (cloning, genome editing, etc.)
- Knowledge in yeast genetics
- Expertise in identification of protein interactions
- General knowledge in proteomics would be a plus
- General knowledge in biochemistry (protein purification, enzymology, etc.).
- Fluent in English
- Scientific communication (presentation and article writing)
- Working with RNA and proteins
- Production and processing of proteomic data is a plus
- Proven ability to plan, drive, implement and conclude research projects with some independence
- Organization and interpretation of scientific results
- Keeping a laboratory notebook and presenting your results
- Friendly, optimistic
- Work in a team
- Motivated, patient, open-minded and good at synthesizing information
- Organised, conscientious, honest
- Critical of results
- Co-supervision of Master students possible
The work will be carried at the Institute of Physical and Chemical Biology (IBPC), a multidisciplinary institute of the Centre National de la Recherche Scientifique (CNRS) located in the historical center of Paris (Latin quarter). Experiments will be led in the host laboratory: UMR8261 “Microbial Gene Expression”, directed by Dr. Ciaran Condon. All the necessary equipment is already in the laboratory or in a very close proximity. The project will be directed by Valérie Heurgué-Hamard (Research Director, CNRS).
Constraints and risks
- It is possible that this research project involves the use of radio isotopes
- A candidate must be in compliance with the mobility rule which stipulates that you have not resided or exercised your main activity (work or studies) in France for more than 12 months during the three years preceding the date of recruitment.
The application should be written in English and submitted to https://emploi.cnrs.fr/. It must include a detailed CV, a minimum of two letters of reference, a cover letter describing your short and long-term career objectives, and a signed declaration that you comply with the mobility rule which stipulates that you have not resided or carried out your main activity (work or studies) in France for more than 12 months during the three years preceding the date of recruitment. The complete file must also be sent to Bruno MIROUX & Magdalena TORTYNA, respectively director and manager of the project at DYNAMOcofund@ibpc.fr. See details on the website http://labexdynamo.ibpc.fr/fp-dynamo-paris/
The position is designed as a first step in a research career, and the evaluation of candidates will be based primarily on their research qualifications and skills that can complement and strengthen ongoing research at the partner institutions.
Step 1. The applications of each eligible candidate will be evaluated by independent international experts within the relevant research theme. Eligible candidates will be evaluated based on merit, motivation for the program, academic excellence, and personal qualifications such as collaboration and communication skills.
Step 2. Up to three candidates will be selected for a video interview with the independent experts for each open position. After the interview, short-listed candidates will be invited to a remote conference with the project director and a DYNAMO board member to define the general scope of the project, training, and research environment. Applicants will be asked to write a 3-page project proposal, contributing their original ideas, and will have 2 weeks to submit it.
Step 3. Each project proposal will be evaluated by one of the independent experts and the DYNAMO board member who evaluated the applicant in the previous steps. Final selection will be made based on the scores obtained in Steps 1, 2, and 3. The minimum score must be above 20/40. The best candidate will be offered the postdoctoral position with a start date of January 1 to April 30, 2023.
The CNRS (Centre National de la Recherche Scientifique) is an equal opportunity employer. In addition, FP-DYNAMO-PARIS is committed to promoting the role of women in science and thus explicitly encourages them to apply.
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