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Content archived on 2024-05-29

Study of the role of notch signaling in controlling cell differentiation and proliferation in the intestinal epithelium

Objective

The goal of the proposed project is to elucidate the mechanisms of action of Notch signalling, by using the mouse intestine as a model for studying cell lineage specification and stem cell renewal. I propose experiments aimed at identifying the molecular factors that can influence the choice between differentiation and proliferation and at testing the hypothesis that Notch might have a key role in controlling the proliferative potential of gut stem cells. The Notch signalling pathway plays a central role in mediating cell fate decisions and patterning in Eukaryotes.

Our preliminary results suggest that experimental manipulation of Notch signals could be a promising avenue to influence the fate of gut stem cells that could be used for cell therapy. I will utilize Cre/Lox mice to activate Notch signalling in the adult intestinal epithelium, to test the hypothesis that sustained Notch signals may contribute to neoplastic transformation of intestinal cells. I will then characterize the nature of the undifferentiated gut progenitors that we have shown to be amplified upon Notch activation.

These experiments are aimed at characterizing the growth and differentiation properties of gut stem cells, in order to develop functional assays that will eventually evaluate their plasticity. I also propose experiments aimed at elucidating the non-cell autonomous effects of Notch signals, as well as at clarifying the interplay between the Notch and the Wnt pathways in controlling gut homeostasis. In parallel with the elucidation of the molecular mechanisms through which Notch signals control intestinal cell fate, this project might contribute to the isolation and characterization of adult gut stem cells, which could be used to develop cell therapy strategies. In addition, one of the objectives of this project aims at the identification of reliable markers for intestinal stem cells, a problem that continues to hamper progress and that remains a priority in this field.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2005-MOBILITY-5
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

INSTITUT CURIE
EU contribution
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Total cost

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