Description du projet
La régulation du cycle cellulaire au cours du développement
L’organisation tissulaire et la taille des organes sont déterminées au cours du développement d’une manière parfaitement synchronisée qui nécessite une orchestration minutieuse du cycle cellulaire. La compréhension des mécanismes qui régissent l’association temporelle du cycle cellulaire et du développement est essentielle à la celle du développement des organes. Le projet DevCycle, financé par l’UE, utilisera le nématode Caenorhabditis elegans comme organisme modèle pour étudier le cycle cellulaire au cours du développement. Les chercheurs créeront une plateforme microfluidique innovante pour visualiser le développement des larves en se concentrant sur les cellules intestinales. L’identification de nouveaux régulateurs qui contrôlent l’expression génétique spécifique à chaque stade fournira un aperçu unique des modèles de division spécifiques aux tissus.
Objectif
Animal development depends on precisely timed cell divisions, which ensure the formation of tissues and organs with specific architectures and functions. As cells differentiate and mature, they need to modify the expression of cell-cycle regulators in order to achieve tissue-specific division patterns. It is largely unknown how cells coordinate cell-cycle gene expression changes with developmental timing and how cell cycles can be altered to give rise to different tissue architectures and organ sizes.
DevCycle will address these questions by studying intestinal cell cycles in nematodes. I have recently pioneered tools to measure mRNA expression changes and chromatin modifications in purified intestinal cells from C. elegans, which we will use to uncover how the expression of cell-cycle genes is changing during development and to identify novel regulators that control stage-specific gene expression. Moreover, I will implement a novel microfluidics platform for long-term imaging of larval development to identify the mechanisms that allow temporal coupling of cell cycle and development. This system will allow us to visualize and manipulate transcription factor gradients that direct intestinal cell cycles, providing unprecedented insights into how cell cycles are timed. Finally, I will analyse the mechanisms that control cell-cycle behaviour in P. redivivus, a related nematode in which intestinal cells undergo a slightly different cell-cycle pattern. Expanding our analyses to this species will empower us to investigate how cell-cycle patterns can diversify to generate phenotypic variability.
Together, this research program will develop a mechanistic understanding of the temporal control of cell cycles in development, revealing new paradigms on how tissue-specific division patterns arise. This knowledge will open up future avenues to modulate cell cycles for tissue engineering purposes, as well as to control cell divisions in disease.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
1011 JV AMSTERDAM
Pays-Bas