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Deciphering A Mechanism Coupling Translation And Rna Decay In Eukaryotes

Reference : PhD Bertrand SERAPHIN

Offer publication : April 6, 2016

The regulation of gene expression is particularly complex in eukaryotic organisms. This essential process allows cells to adapt to changing conditions and / or differentiate. This control occurs mainly by changes in transcription or degradation of messenger RNA that allow the synthesis in greater or lesser quantity of proteins needed by the cell.

Our work on the degradation of messenger RNAs enabled us to characterize several proteins involved in a critical step of this process. Unexpectedly, our experimental data revealed an interaction of these factors with a protein complex associated with the translational machinery. The validation of this
link would allow us to understand how cells can coordinate translation efficiency with the stability of the corresponding mRNA.

We propose to first develop the analysis of this process using the yeast S. cerevisiae as a model system because it will facilitate initial studies at the genetic and physiological levels. Protein-protein interaction studies based on several strategies (recombinant proteins, two-hybrid ...) will be used to define and validate the contact occurring between these factors. If possible, structural information will be obtained with a collaborating team. In parallel, the validation of the biological role of these interactions will be done through in vitro assays (activity tests...) and in vivo (characterization of mutants, analyses of reporter genes...).

This project is expected to provide a molecular and functional understanding of a new protein complex involved at the interface of translation and degradation of messenger RNA and to determine its role in cellular function. In particular, the involvement of such a process in a new quality control mechanism eliminating poorly translated mRNAs will be explored. Finally, the evolutionary conservation of this process in humans, its impact on the production of human proteins, and its involvement in certain diseases will be studied.

- WISHED SKILLS : The candidate will have a good knowledge of general mechanisms used by living organisms as well as of molecular and cellular biology, genetics and biochemistry. Skills in biocomputing would be an advantage. A deep interest for experimental analyses, a strong motivation and a good capacity for team work in a multidisciplinary environment are also important. Written and spoken English will be necessary for communication in the team and with other groups. An open mind will be required to understand alternative approaches and the latest strategies (structural analyses, high-throughput studies...).

- EXPERTISES WHICH WILL BE ACQUIRED DURING THE TRAINING : The training will be centered on the learning of methods and techniquesrequired to decipher in a synthetic manner a biological process using approaches ranging from biochemical assays to in vivo large scale analyses. An
important point will be the integration of complementary approaches necessary to understand a biological system. Expertise gained during the PhD will include training for oral and written communication (regular team meeting, institute seminars, writing of articles...), training to organize the work at the
individual and team levels, and learning on how to use new equipment.

Your application

Application Deadline : Dec. 31, 2016

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