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Habilitation à diriger des recherches

Etude de nouveaux aspects liés à la machinerie traductionnelle : amidotransférases et aminoacyl-ARNt synthétases.

Abstract : My various research topic concern the translation of the genetic information that can be considered as the production of biomolecules whose role in a cell can be either structural or functional. First I studied the process of tRNA aminoacylation and the formation of modified bases within the tRNA molecule. Indeed, the tRNA plays q key role during protein synthesis because the precision of its aminoaclylation will be crucial for the translation fidelity.
In yeast, one can find a simplified version of the multisynthetase complex that consists of MetRS, GluRS and Arc1p, a protein encoded by a gene that is not only in genetic interaction with the nucleocytoplasmic transport machinery but also with genes involved in tRNA biogenesis. These studies brought me to study the role of MTR10 in nucleocytoplasmic exchanges and a possible role of this gene in tRNA transport. The techniques I used during this study were also helpful for the study of Efl1p, an EF-2 type GTPase involved in a late cytoplasmic step of 60S ribosomal subunit biogenesis.
All my previous work allowed me to gain some experience with various biochemical and genetic techniques that will be very helpful for my future work that deals with the systematic study of the localisation and interaction of aminoacyl-tRNA synthetases. Indeed, it is not conceivable that the tRNA/aminoacyl-tRNA synthetases are completely autonomous in a cell but they have rather to interact / communicate with the other partners of the translational machinery and most likely with other factors involved in various cellular pathways.
Another aspect of my project, still related to tRNA aminoacylation, concerns an atypical system of aminoacyl-tRNA formation in the asparagine and glutamine systems. Indeed, a large number of prokaryotes, including human pathogens, do not posses genes coding for asparaginyl- and/or glutaminyl-tRNA synthetases and therefore use an atypical indirect pathway for tRNA aminoacylation. The study of these mechanisms is not interesting only at the level of evolution and structure function relationship but also at the level of public health because inhibiting these atypical aminoacylation pathways will deliver new classes of antibiotics. This aspect is really crucial since the resistance of many pathogens to more classical antibiotics begins to become an enormous health problem.
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Habilitation à diriger des recherches
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Bruno Senger. Etude de nouveaux aspects liés à la machinerie traductionnelle : amidotransférases et aminoacyl-ARNt synthétases.. Sciences du Vivant [q-bio]. Université Louis Pasteur - Strasbourg I, 2006. ⟨tel-00270801⟩

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