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Spatio-temporal coupling between transcription and translation dynamics during development

Description du projet

Découvrir les mécanismes cachés qui régissent la formation de modèles au cours du développement

Au cours du développement, le contrôle précis de l’expression des gènes permet l’établissement reproductible de modèles, menant à la formation des organes au bon moment et au bon endroit. L’établissement des modèles de développement a essentiellement été étudié au niveau transcriptionnel. Le sort de ces transcriptions n’a quant à lui suscité que peu d’intérêt jusqu’à présent. De nouvelles méthodes permettant d’étudier la traduction de molécules d’ARNm uniques ont révélé une hétérogénéité critique dans la traduction. Le projet LightRNA2Prot, financé par l’UE, cherchera à décrypter les mécanismes qui dictent la précision de l’expression des gènes. Pour ce faire, il examinera simultanément les deux couches de régulation que constituent la transcription et la traduction, ainsi que leur couplage potentiel.

Objectif

During development, precise control of gene expression allows the reproducible establishment of patterns, leading to the adoption of cellular identities at the right time and place. What are the mechanisms behind such precision? To date, this question has been primarily examined from the focal point of transcription. However, precision in mRNA production is functionally relevant only if it leads to precision in protein expression. While the linear correlation between the levels of a given mRNA and the amount of protein it encodes has been assumed for the last six decades within the central dogma of molecular biology, many examples challenge this view. The control of translation, particularly in distinct subcellular compartments where mRNA are targeted, may lie at the heart of this mRNA to protein disconnect. LightRNA2Prot aims to unravel the mechanisms underlying the lack of correlation between mRNA and proteins levels to elucidate the sources of reproducible cell fate decisions during development. Importantly, it considers both the layers of regulation constituted by transcription and translation respectively, as well as their potential coupling. We will use quantitative imaging methods that simultaneously monitor mRNA, nascent peptides, and protein in Drosophila living embryos, combined with genetic/optogenetic manipulations to dissect the mechanisms at play. LightRNA2Prot focuses on two key questions: 1-How do the translation dynamics of key localized developmental transcripts modulate precise patterning? 2-How are (co)-transcriptional nuclear events coordinated with translational control in space and time? Combined with mathematical modeling and phenotypic characterization, our quantitative approaches will provide a dynamic multiscale view of gene expression control in vivo. The novel integration of translational control has the potential to dramatically change our view of stereotypic pattern formation and reproducible cell fate decisions during development.

Institution d’accueil

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Contribution nette de l'UE
€ 2 000 000,00
Adresse
RUE MICHEL ANGE 3
75794 Paris
France

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Région
Ile-de-France Ile-de-France Paris
Type d’activité
Research Organisations
Liens
Coût total
€ 2 000 000,00

Bénéficiaires (1)