Descrizione del progetto
La regolazione del ciclo cellulare nel corso dello sviluppo
L’architettura dei tessuti e le dimensioni degli organi vengono determinate nel corso dello sviluppo con una tempistica perfetta, che richiede un’attenta orchestrazione del ciclo cellulare. La comprensione dei meccanismi alla base dell’associazione temporale del ciclo cellulare e dello sviluppo è fondamentale per comprendere lo sviluppo degli organi. Il progetto DevCycle, finanziato dall’UE, impiegherà il nematode Caenorhabditis elegans come organismo modello per studiare il ciclo cellulare nel corso dello sviluppo. I ricercatori creeranno una nuova piattaforma microfluidica per effettuare l’immaginografia dello sviluppo larvale prestando particolare attenzione alle cellule intestinali. L’individuazione dei nuovi regolatori che controllano l’espressione genica a fase specifica fornirà indizi inediti sui modelli di divisione tessuto-specifici.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
1011 JV AMSTERDAM
Paesi Bassi