Descripción del proyecto
El papel de la nutrición sobre las células madre tisulares
Los tejidos contienen una pequeña subpoblación de células denominadas células madre tisulares, que se diferencian para reforzar la renovación tisular por daños y mantener la homeostasis. Nuevas pruebas indican que la nutrición desempeña un papel fundamental en la función de estas células madre tisulares, especialmente en el intestino. STELLA es un proyecto financiado con fondos europeos que se centrará en la proteína triptófano periódico 1 (PWP1), que responde a la señalización de nutrientes y se sabe que se une a la cromatina. Los investigadores del proyecto emplearán «Drosophila melanogaster» como organismo modelo para estudiar el papel de PWP1 en las células madre y el envejecimiento. Los resultados aportarán conocimientos importantes sobre la regulación dependiente de nutrientes de las células madre y su pertinencia en el envejecimiento.
Objetivo
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 Our unpublished data shows that PWP1 has a role in intestinal stem cell regulation, downstream of Insulin signalling, and that it has a significant impact on organismal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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
00014 Helsingin Yliopisto
Finlandia