Descrizione del progetto
Indizi sulle nicchie di cellule staminali per la salute dello scheletro
Le cellule staminali sono cellule specializzate in grado di produrre qualsiasi tipologia cellulare all’interno di un tessuto o di un organo, contribuendo al loro mantenimento e riparazione. Finanziato dal Consiglio europeo della ricerca, il progetto MERLIN sta approfondendo le cellule staminali dello scheletro e l’impatto esercitato dall’alterazione della nicchia in cui risiedono a causa di lesioni o invecchiamento. Basandosi sulla precedente identificazione di un nuovo tipo di nicchia cellulare per lo scheletro, il progetto mira a studiare il profilo metabolico di queste cellule e la regolazione delle loro vie metaboliche. I risultati di MERLIN dispongono delle potenzialità di consentire lo sviluppo di interventi basati sulle cellule staminali volti a migliorare la salute dello scheletro.
Obiettivo
"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."
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
601 77 Brno
Cechia