Project Details
Projekt
Understanding the dynamic interplay of altered calcium signaling and actin remodeling in podocytes in FSGS using in vivo imaging
Applicant
Dr. Matthias Johannes Hackl
Subject Area
Nephrology
Term
since 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 386793560
Loss of podocytes is central to the development of focal segmental glomerulosclerosis (FSGS) and results in hypertrophy of neighboring podocytes to maintain the filtration barrier. However, the effectiveness of hypertrophy is limited and once podocyte loss exceeds the threshold of 20 %, this will result in glomerular sclerosis. For the adjustment of podocytes to hypertrophy, struggling to maintain the elaborate podocyte architecture and to prevent detachment from the basement membrane, the dynamic capacities of the actin cytoskeleton are of prime importance. Hence, in this research proposal we will address the seminal question of how the interplay of altered calcium signaling and the reorganization of the actin cytoskeleton jointly contribute to glomerular pathophysiology and to progression towards FSGS. Therefore, we will employ a state-of-the-art imaging approach including intravital multiphoton microscopy, innovative reporter mouse models, serial multiphoton imaging and super-resolution technologies. The overarching goal of this research proposal is to understand the pathogenetic effect of calcium signaling and its impact on alterations of the actin cytoskeleton in podocytes. Specifically, we will (1) characterize the interconnection of intracellular calcium levels and actin remodeling during podocyte hypertrophy, (2) study the impact of Angiotensin II type 1 receptors on calcium homeostasis and signaling in podocytes, and (3) use optogenetic tools to trigger a constitutive calcium entry in podocytes, characterize the involved ion channels and visualize the effect on the actin cytoskeleton in vivo.
DFG Programme
Clinical Research Units
