Project 1 - CaSR-mediated signalling in colonocytes.

Host Institution: Medical University of Vienna

Hypothesis: The pathways activated by CaSR ligands present in the gut (e.g. aromatic amino acids or polyamines) are distinct from those in other tissues, such as parathyroid.

Objectives: To identify colon-specific signalling pathways driven by the CaSR and to study the consequences of losing CaSR expression in the colon. ESR_MUW1 will 1) Examine how “intestine-specific” ligands (L-Phe, poly-Arg or spermine) affect Ca²⁺-driven CaSR signalling pathways; 2) Test the impact of calcimimetics/calcilytics on the choice of downstream pathways: such as intracellular Ca²⁺ oscillations, cAMP or IP3 accumulation using the HTRF technology, impact on protein kinase activation by reverse-phase protein array or in-cell western blot;. 3) Study the effect of the New Western Diet (NWD): high in fat low in fibre, folate, calcium and vitamin D on the development of premalignant lesions in mice lacking the CaSR in the intestine.