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Project

Analysis of Calcium signaling in autosomal dominant polycystic kidney disease.

Mutations in the genes encoding the polycystin-1 and -2 proteins lead to autosomal dominant polycystic kidney disease (ADPKD), the most common inherited renal disease. The molecular mechanisms underlying the formation of renal cysts are poorly characterized, although better knowledge of these mechanisms could have important therapeutic consequences. In this project, we aim to identify how polycystin mutations affects cellular signaling events. We will in particular focus on calcium signaling, as it is postulated that disturbed calcium homeostasis is a primary event in cystogenesis. We will use kidney epithelial cells obtained from healthy and ADPKD genotyped donors carrying mutations in PKD1 (WP1) and screen these cells for the functional expression of various calcium coupled G-protein coupled receptors (WP2). Further, we will dissect observed calcium signals in detail to identify key molecular players that affect calcium signaling in ADPKD (WP3). As a final step, we will investigate whether modulation of the identified aberrant calcium signaling pathways can prevent or delay cyst formation in human epithelial cells from ADPKD donors via a 3D cell culture system (WP4). We anticipate to be able to provide new insights in the fundamental molecular mechanisms underlying ADPKD, useful for the development of novel treatment strategies.
 

Date:15 Nov 2018 →  11 Feb 2022
Keywords:ADPKD, Calcium signaling, Ion channels, Kidney disease, GPCR receptors
Disciplines:Cell signalling, Cell physiology, Kidney diseases
Project type:PhD project