Project description
Unravelling hidden mechanisms underlying pattern formation during development
During development, precise control of gene expression allows the reproducible establishment of patterns, leading to the formation of organs at the right time and place. The establishment of developmental patterns has been primarily studied at the transcriptional level. By comparison, the fate of these transcripts has hitherto received little attention. New methods enabling the study of the translation of single mRNA molecules revealed a critical heterogeneity in translation. The EU-funded LightRNA2Prot project will seek to decipher the mechanisms dictating precision in gene expression. To this end, it will simultaneously consider both layers of regulation constituted by transcription and translation as well as their potential coupling.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
75794 Paris
France