STELLA | Nutrient regulation of intestinal stem cells – exploring a novel mechanism with relevance to aging

Summary
Tissues of animals undergo constant renewal. This is enabled by pools of tissue-resident stem cells that differentiate to replace aged cells and maintain homeostasis. However, stem cell self-renewal and differentiation capacities gradually start to decline during aging, leading to compromised organ function. Nutrition has a prominent effect on aging and the maintenance of stem cell function. Therefore, investigating the mechanisms responsible for nutrient regulation of tissue stem cells is of direct relevance to understanding the regulatory basis of animal lifespan.
The proposed project will focus on the intestine, which undergoes high cellular turnover and adaptability in response to changing nutrition, and as such is an optimal model for nutrient regulation of tissue stem cells. The use of Drosophila provides advantages including the availability of a powerful genetic toolkit, a short lifespan and the ability to quantitatively analyse stem cell function at the organ-wide level. Specifically, my project will address the regulatory role and physiological relevance of Periodic tryptophan protein 1 (PWP1), a conserved chromatin-binding protein that acts downstream of nutrient-responsive Insulin/mTOR signalling. PWP1 is known to be implicated in embryonic and germline stem cell regulation, but its role in somatic stem cells and aging has remained unexplored. Our unpublished data shows that PWP1 has a role in intestinal stem cell regulation, downstream of Insulin signalling, and that it has a significant impact on organismal lifespan.
The results obtained in this study will go beyond the current knowledge of nutrient-dependent regulation of intestinal stem cells, and will push the boundaries of scientific research on stem cell aging, with substantial societal relevance for the aging population. Along with its scientific objectives, the proposed project has been designed to support my professional development and my career goal of scientific independence.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101028177
Start date: 01-03-2022
End date: 29-02-2024
Total budget - Public funding: 190 680,96 Euro - 190 680,00 Euro
Cordis data

Original description

Tissues of animals undergo constant renewal. This is enabled by pools of tissue-resident stem cells that differentiate to replace aged cells and maintain homeostasis. However, stem cell self-renewal and differentiation capacities gradually start to decline during aging, leading to compromised organ function. Nutrition has a prominent effect on aging and the maintenance of stem cell function. Therefore, investigating the mechanisms responsible for nutrient regulation of tissue stem cells is of direct relevance to understanding the regulatory basis of animal lifespan.
The proposed project will focus on the intestine, which undergoes high cellular turnover and adaptability in response to changing nutrition, and as such is an optimal model for nutrient regulation of tissue stem cells. The use of Drosophila provides advantages including the availability of a powerful genetic toolkit, a short lifespan and the ability to quantitatively analyse stem cell function at the organ-wide level. Specifically, my project will address the regulatory role and physiological relevance of Periodic tryptophan protein 1 (PWP1), a conserved chromatin-binding protein that acts downstream of nutrient-responsive Insulin/mTOR signalling. PWP1 is known to be implicated in embryonic and germline stem cell regulation, but its role in somatic stem cells and aging has remained unexplored. Our unpublished data shows that PWP1 has a role in intestinal stem cell regulation, downstream of Insulin signalling, and that it has a significant impact on organismal lifespan.
The results obtained in this study will go beyond the current knowledge of nutrient-dependent regulation of intestinal stem cells, and will push the boundaries of scientific research on stem cell aging, with substantial societal relevance for the aging population. Along with its scientific objectives, the proposed project has been designed to support my professional development and my career goal of scientific independence.

Status

CLOSED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships