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Metabolic regulation of cell cleavages in early embryogenesis

Description du projet

Les mécanismes métaboliques du développement embryonnaire

Après la fécondation, le zygote subit de nombreux clivages ou divisions cellulaires rapides pour former l’embryon. Cette phase précoce intègre des signaux intrinsèques et extrinsèques aux cellules, mais les mécanismes précis qui facilitent l’adaptation à l’environnement en rapide évolution demeurent en grande partie inconnus. Financé par le programme Actions Marie Skłodowska-Curie, le projet MetEmbryoniC se propose d’étudier le rôle du métabolisme en tant que régulateur essentiel de la dynamique du cytosquelette et de la fonction cellulaire. Les chercheurs feront la lumière sur l’activité métabolique spatio-temporelle et détermineront les influences métaboliques sur la régulation du cytosquelette. Les résultats du projet permettront non seulement de faire avancer les connaissances relatives au développement embryonnaire, mais également de faire la lumière sur les maladies liées au métabolisme, telles que le cancer.

Objectif

Multicellular animals development begins with a sequence of rapid cell cycles and divisions, named ‘cleavages’, leading to the generation of a large pool of cells, from which the embryo develops. While there are several species-specific types of cleavages, the underlying processes of cell-cycle and cytokinesis, involving characteristic large-scale cytoskeletal reorganizations, are well conserved. Yet, how these processes integrate cell-intrinsic and -extrinsic signals, adapting to the rapidly changing environment of the developing embryo, remains largely unknown. An emerging concept implies cell metabolism as an important factor regulating cytoskeletal elements and, hence, cellular function. Here, I test the hypothesis that during cleavages, specific metabolic elements play an essential role in regulating the cytoskeleton.
To address this hypothesis, I developed an innovative fluxomics approach for analyzing whole-embryo metabolism, combining metabolomics, transcriptomic, and real-time bioenergetics measurements in two different embryonic cleavage pattern models: ascidians and zebrafish. By combining the Heisenberg group's expertise in biomechanics and my expertise in metabolism, I will follow three main lines of research based on the whole-embryo fluxomics data: (1) Characterizing the spatiotemporal metabolic activity in the cleaving embryo; (2) analyzing the function of specific metabolic elements in cytoskeleton regulation during cleavages; and (3) determining the extrinsic factors (temperature and oxygen levels) affecting the mechano-metabolic reactions during cleavages. I expect these findings to provide insight into mechano-metabolic mechanisms that will advance our understanding of embryonic development and shed light on disease-related processes where metabolism and cell division are highly interconnected, such as cancer.

Coordinateur

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Contribution nette de l'UE
€ 199 440,96
Adresse
Am Campus 1
3400 Klosterneuburg
Autriche

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Région
Ostösterreich Niederösterreich Wiener Umland/Nordteil
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée