Dynamique et régulation de la traduction des ARNm dans le développement embryonnaire précoce // Dynamics of translational control in early embryonic development

Early embryogenesis relies on the use of maternally stored mRNA in the cytoplasm and as such, highly depends on translational regulation. Proper and timely translation of maternal mRNAs is required for correct embryogenesis (Teixiera and Lehmann, 2019). Sea urchin embryos offer an elegant model to elucidate the network of actors involved in translational control during early development. The overall rate of protein synthesis is low in unfertilized eggs and fertilization triggers a dramatic rise in protein synthesis, dependent on mTOR pathway and necessary for the onset of cell divisions (Cormier et al, 2016; Pontheaux et al, 2021). Comparison of polysomal associated mRNA (i.e translated) between unfertilized eggs versus fertilized embryos using next-generation sequencing provides an approach to a genomic-wide investigation of translation dynamics at fertilization and during the first cell cycles of development. We have identified polysome-recruited and polysome-released mRNA by polysome profiling, and showed that only a subset of maternal mRNAs is translated at fertilization before the onset of the first cell division (Chassé et al, 2018). This translated subset shows selective enrichment in functional categories, such as cell cycle regulators. How are the remaining maternal mRNAs used during subsequent cell cycles, before the maternal-to-zygotic transition? How do the signalling pathways activated at fertilization impact and interact on polysomal recruitment? What are the cis- and trans-regulatory elements that convey specific translation to mRNAs?
The project will aim at determining the dynamics of polysome profiling, and characterize the consensus regulatory elements within the co-regulated mRNAs, in the context of early embryogenesis.
The analysis of translatomes at different time points following fertilization will provide information on the dynamics and orchestration of polysomal recruitment. The role of signalling pathways will be explored by analyzing polysomal recruitment in presence of mTOR and cell cycle inhibitors. An ongoing collaboration with Dr Juliana Silva Bernardes (AD2M, SBR) is currently aiming at identifying enriched consensus RNA motifs within co-translated mRNAs using machine learning computational approaches. The search for the motifs involved in polysomal recruitment common to translated mRNAs will allow to identify the cis regulatory elements present in the 5' and/or 3'UTR regions, as well as the trans regulatory elements, e.g. proteins associated with common motifs. We are also using Nanopore direct RNA sequencing to identify potential features related with the translational status of mRNAs such as specific isoforms or epitranscriptomics marks, in collaboration with Genomer Plateform of the SBR and the CMAR functional genomics service of our unit. The regions/features identified will be tested for their ability to drive translation of a reporter mRNA microinjected into sea urchin eggs (as described in Chassé et al, 2019).
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Early embryogenesis relies on the use of maternally stored mRNA in the cytoplasm and as such, highly depends on translational regulation. Proper and timely translation of maternal mRNAs is required for correct embryogenesis (Teixiera and Lehmann, 2019). Sea urchin embryos offer an elegant model to elucidate the network of actors involved in translational control during early development. The overall rate of protein synthesis is low in unfertilized eggs and fertilization triggers a dramatic rise in protein synthesis, dependent on mTOR pathway and necessary for the onset of cell divisions (Cormier et al, 2016; Pontheaux et al, 2021). Comparison of polysomal associated mRNA (i.e translated) between unfertilized eggs versus fertilized embryos using next-generation sequencing provides an approach to a genomic-wide investigation of translation dynamics at fertilization and during the first cell cycles of development. We have identified polysome-recruited and polysome-released mRNA by polysome profiling, and showed that only a subset of maternal mRNAs is translated at fertilization before the onset of the first cell division (Chassé et al, 2018). This translated subset shows selective enrichment in functional categories, such as cell cycle regulators. How are the remaining maternal mRNAs used during subsequent cell cycles, before the maternal-to-zygotic transition? How do the signalling pathways activated at fertilization impact and interact on polysomal recruitment? What are the cis- and trans-regulatory elements that convey specific translation to mRNAs?
The project will aim at determining the dynamics of polysome profiling, and characterize the consensus regulatory elements within the co-regulated mRNAs, in the context of early embryogenesis.
The analysis of translatomes at different time points following fertilization will provide information on the dynamics and orchestration of polysomal recruitment. The role of signalling pathways will be explored by analyzing polysomal recruitment in presence of mTOR and cell cycle inhibitors. An ongoing collaboration with Dr Juliana Silva Bernardes (AD2M, SBR) is currently aiming at identifying enriched consensus RNA motifs within co-translated mRNAs using machine learning computational approaches. The search for the motifs involved in polysomal recruitment common to translated mRNAs will allow to identify the cis regulatory elements present in the 5' and/or 3'UTR regions, as well as the trans regulatory elements, e.g. proteins associated with common motifs. We are also using Nanopore direct RNA sequencing to identify potential features related with the translational status of mRNAs such as specific isoforms or epitranscriptomics marks, in collaboration with Genomer Plateform of the SBR and the CMAR functional genomics service of our unit. The regions/features identified will be tested for their ability to drive translation of a reporter mRNA microinjected into sea urchin eggs (as described in Chassé et al, 2019).
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Début de la thèse : 01/10/2025

Contrat doctoral

Concours pour un contrat doctoral

Sorbonne Université SIM (Sciences, Ingénierie, Médecine)

515 Complexité du vivant

Candidates should have a strong background in molecular and cellular biology, and should be highly motivated. Previous experience in RNA maipulation, bioinfomatic analysis of RNA sequences, and in marine organisms handling and microinjection would be an advantage. Good knowledge of the English language (both written and spoken) is also required.
Candidates should have a strong background in molecular and cellular biology, and should be highly motivated. Previous experience in RNA maipulation, bioinfomatic analysis of RNA sequences, and in marine organisms handling and microinjection would be an advantage. Good knowledge of the English language (both written and spoken) is also required.