- Project 1 - CaSR-mediated signalling in colonocytes
- Project 2 - Evaluation of CaSR - based therapeutics in prevention of tumourigenesis and metastatic potential in colorectal cancer
- Project 3 - Role of the CaSR in inflammatory lung diseases
- Project 4 - Evaluation of CaSR-targeted drugs for the treatment of neuroblastoma
- Project 5 - Delineation of CaSR signalling in primary cells and cell lines with native receptor expression
- Project 6 - Role of the calcium-sensing receptor (CaSR) in glucose homeostasis
- Project 7 - Cell-specific CaSR signaling
- Project 8 - Targeting CaSR in human skeletal muscle cells to delay sarcopenia development
- Project 9 - Evaluation of CaSR-targeted drugs for the treatment of diabetes mellitus
- Project 10 - Role of the CaSR in early bone metastasis of breast cancer cells and evaluation of CaSR - based therapeutics in prevention or delay of metastasis formation
- Project 11 - Ligand-biased G-protein activation by CaSR
- Project 12 - The role of CaSR in AD pathomechanisms
- Project 13 - In silico analysis of CaSR-ligand interaction
- Project 14 -Generation, validation and application of algorithms for tissue segmentation used in advanced tissue cytometry
Project 12 - The role of CaSR in AD pathomechanisms
Host Institution: Biotalentum Ltd
» Info
Hypothesis: CaSR activation is a key event in AD associated amyloid-beta induced neuronal death.
Objectives: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease affecting nearly 30 million people worldwide. Amyloid-beta induces cell loss in the nervous system both in vitro and in vivo. Amyloid-beta binds to and activates CaSR, which leads to the generation of Reactive Oxygen Species and Peroxynitrite, which subsequently induce oxidative damage and cell death. Blockers of CaSR prevent amyloid-beta toxicity. To identify the role of CaSR in pathomechanism of AD ESRBIOT will 1) Develop hIPSC derived neuronal cell cultures from at least 2 clinically identified AD patients and an age-matched control. In these cell cultures ESRBIOT will determine the expression level of CaSR and CaSR-mediated signalling by using functional readouts (electrophysiology, stimulated Ca2+ influx assay), ESRBIOT will also test whether blocking CaSR will normalise AD-related in vitro phenotypes. 2) Determine the effect of amyloid-beta challenge on the AD and control hIPSC derived neuronal cell cultures by using functional readouts and toxicity assays. ESRBIOT will test the effect of CaSR blockers on prevention of amyloid-beta induced toxicity.
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