Project description
Insight into stem cell niches for skeletal health
Stem cells are specialised cells capable of producing all cell types within a tissue or organ, contributing to organ maintenance and repair. Funded by the European Research Council, the MERLIN project is researching into stem cells of the skeleton and the impact of disrupting the niche where stem cells reside due to ageing or injury. Capitalising on the previous identification of a novel niche cell type for the skeleton, the project aims to study the metabolic profile of these cells and the regulation of their metabolic pathways. Project findings can potentially lead to the development of stem cell-based interventions that enhance skeletal health.
Objective
"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."
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
601 77 Brno
Czechia