Projektbeschreibung
Verborgene Mechanismen der Musterbildung im Lauf der Entwicklung enträtseln
Während der Entwicklung dient die präzise Steuerung der Genexpression der reproduzierbaren Festlegung von Mustern, welche die Bildung von Organen zur richtigen Zeit und am richtigen Ort bewirken. Die Erstellung von Entwicklungsmustern wurde hauptsächlich auf der Transkriptionsebene untersucht. Im Vergleich dazu ist dem Schicksal dieser Transkripte bisher wenig Aufmerksamkeit gewidmet worden. Neue Methoden, mit denen die Translation einzelner mRNS-Moleküle untersucht werden kann, offenbarten eine kritische Heterogenität in der Translation. Das EU-finanzierte Projekt LightRNA2Prot wird die Mechanismen enträtseln, welche die Präzision der Genexpression bestimmen. Zu diesem Zweck werden beide Ebenen der Regulation, gebildet durch Transkription und Translation, sowie ihre mögliche Kopplung gleichzeitig betrachtet.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
ERC - Support for frontier research (ERC)Gastgebende Einrichtung
75794 Paris
Frankreich