Description du projet
Étudier les niches des cellules souches pour améliorer la santé du squelette
Les cellules souches sont des cellules spécialisées capables de produire tous les types de cellules d’un tissu ou d’un organe, contribuant ainsi à l’entretien et à la réparation de cet organe. Financé par le Conseil européen de la recherche, le projet MERLIN étudie les cellules souches du squelette et l’impact de la perturbation de la niche dans laquelle elles résident en raison du vieillissement ou d’une blessure. Capitalisant sur l’identification antérieure d’un nouveau type de cellule de niche pour le squelette, le projet vise à étudier la régulation des voies et le profil métaboliques de ces cellules. Les résultats du projet sont susceptibles d’ouvrir la voie au développement d’interventions basées sur les cellules souches qui amélioreront la santé globale du squelette.
Objectif
"The continued health of many of our organs, including the skeleton, relies on the function of specialized stem cells. These stem cells reside in niches that support their long-term maintenance. Disruption of the niche due to aging, injury, or genetic mutations, can lead to declines in stem cells and a failure to maintain and repair tissues. Compared to our understanding of the stem cells that maintain and repair our skeleton, we know much less about the cell types that constitute their niche. My prior large-scale genomics studies have uncovered a novel niche cell type for the skeleton. Intriguingly, these niche cells are defined by a unique metabolic profile, highlighting in particular enzymes for Phenylalanine (Phe) / Tyrosine (Tyr) metabolism and glycogen synthesis. Traditionally, it has been thought that Phe/Tyr are degraded primarily in the liver, and the skeletal malformations in patients with Phenylketonuria (mutation in PAH), Tyrosinemia (I-III, mutations in FAH, TAT, HPD) and Alkaptonuria, a.k.a. ""black bone disease"" (mutation in HGD) has been interpreted as the results of systemic intoxication by accumulated metabolites. My dogma-shattering result suggests that local regulation of Phe/Tyr degradation might be a critical strategy to support the skeleton. I will establish a research group that leverages the powerful genomic, genetic, and high-resolution imaging strengths of zebrafish to test the requirements of niche cells in skeletal stem cells homeostasis and the roles of metabolism in stem cell maintenance. Findings from my proposed studies will inform future therapies aimed at correcting metabolic diseases and restoring stem cell function and skeletal health by modulating the niche."
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
601 77 Brno
Tchéquie