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Metabolic regulation of the skeletal stem cell niche

"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 agin... ver más

31/12/2028

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

Masarykova univerzita No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-11-27

ERC-2023-STG: ERC STARTING GRANTS Scope:Objectives

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Cerrada hace 2 años

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1 Participantes

1.50M€ | Lider

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Duración del proyecto: 61 meses Fecha Inicio: 2023-11-27
Fecha Fin: 2028-12-31

Líder del proyecto

Masarykova univerzita No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto "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."

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