Grant: Project Grant
McGill University
$1,048,050.00
Allosteric activation of the alkaline phosphatase TNAP: from basic biology to therapeutic potential
EF 2024-25
Résumé
Metabolites relay physiological signals that help cells respond to their environment by regulating protein functions. Tissue non-specific alkaline phosphatase (TNAP) is required for the conversion of chemical energy into heat by adipocytes (thermogenesis) by hydrolyzing phosphocreatine, and it is necessary to support bone mineralization by hydrolyzing the mineralization inhibitor pyrophosphate. No endogenous TNAP regulators are known, and how its activity changes in response to dynamic metabolic changes remains poorly understood. We have recently discovered one endogenous TNAP regulator. In this proposal, we will characterize how this regulator activates TNAP with the final goal of leveraging this information to develop TNAP activators for therapeutic purposes in treating overnutrition and mineralization disorders.
Programme
Project Grant
Bénéficiaire
Emplacement
Quebec, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
CIHR Funding Decisions Database
Tel que publié
Id
507722
Name
Kazak Lawrence
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Musculoskeletal Health and Arthritis
Theme2
Biomedical
Prcname2
Cell Biology - Disease 2
Projecttitle
Allosteric activation of the alkaline phosphatase TNAP: from basic biology to therapeutic potential
Programtype2
Operating Grants
Orgnameinp2
McGill University
Cihramount2
$1,048,050
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Bioenergetics; Bone Mineralization; Creatine; Enzyme Kinetics; Glycerol; Phosphocreatine; Protein Purification; Protein Structure; Thermogenesis; Tissue Nonspecific Alkaline Phosphatase
Abstract
Metabolites relay physiological signals that help cells respond to their environment by regulating protein functions. Tissue non-specific alkaline phosphatase (TNAP) is required for the conversion of chemical energy into heat by adipocytes (thermogenesis) by hydrolyzing phosphocreatine, and it is necessary to support bone mineralization by hydrolyzing the mineralization inhibitor pyrophosphate. No endogenous TNAP regulators are known, and how its activity changes in response to dynamic metabolic changes remains poorly understood. We have recently discovered one endogenous TNAP regulator. In this proposal, we will characterize how this regulator activates TNAP with the final goal of leveraging this information to develop TNAP activators for therapeutic purposes in treating overnutrition and mineralization disorders.
Competitiondate
202409
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Kazak, Lawrence
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $1,048,050~ $0~
