Informace o projektu
Vztah struktury a funkce v signálováni fibroblastových růstových faktorů
- Kód projektu
- GF21-26400K
- Období řešení
- 1/2021 - 12/2023
- Investor / Programový rámec / typ projektu
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Grantová agentura ČR
- LA granty
- Lead agentura
- Fakulta / Pracoviště MU
- Lékařská fakulta
- Spolupracující organizace
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Uniwersytet Wrocławski
Fibroblast growth factors (FGFs) interact with four types of cell surface receptors (FGFRs) to deliver signals critical for development and functioning of mammalian organs. FGFs trigger proliferative, migrational, anti-apoptotic and metabolic signaling, representing an attractive therapeutic option for tissue regeneration, metabolic syndromes and aging. Such use is however complicated by our poor knowledge of the molecular basis of FGF signaling. How a particular FGF regulates diverse cell responses is not known, and is the subject of the proposal. We will study the structure-function relationship of FGFs by engineering four members of FGF family, FGF8, FGF9, FGF10 and FGF18. We will obtain mutants with increased thermal stability and modified ability to interact with FGFRs and heparan sulphate. These FGF variants will be tested in cells for their ability to activate different types of signaling. The proposed research will unravel structural and biophysical properties of FGFs, which drive the specific cell response.
Cíle udržitelného rozvoje
Masarykova univerzita se hlásí k cílům udržitelného rozvoje OSN, jejichž záměrem je do roku 2030 zlepšit podmínky a kvalitu života na naší planetě.
Publikace
Počet publikací: 6
2024
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Discovery of Two Highly Selective Structurally Orthogonal Chemical Probes for Activin Receptor-like Kinases 1 and 2
Journal of Medicinal Chemistry, rok: 2024, ročník: 67, vydání: 15, DOI
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Ligand bias underlies differential signaling of multiple FGFs via FGFR1
elife, rok: 2024, ročník: 12, vydání: April 2024, DOI
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Quantitative and qualitative differences in the activation of a fibroblast growth factor receptor by different FGF ligands
CYTOKINE & GROWTH FACTOR REVIEWS, rok: 2024, ročník: 78, vydání: August 2024, DOI
2023
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Skeletal diseases caused by mutations in PTH1R show aberrant differentiation of skeletal progenitors due to dysregulation of DEPTOR
Frontiers in Cell and Developmental Biology, rok: 2023, ročník: 10, vydání: January 2023, DOI
2022
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Expanding horizons of achondroplasia treatment: current options and future developments
Osteoarthritis and Cartilage, rok: 2022, ročník: 30, vydání: 4, DOI
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LuminoCell: a versatile and affordable platform for real-time monitoring of luciferase-based reporters
Life science alliance, rok: 2022, ročník: 5, vydání: 8, DOI