Address of the institution:
Loss of podocytes is central to the development of focal segmental glomerulosclerosis (FSGS) and results in hypertrophy of neighbouring podocytes to maintain the filtration barrier. This leads to increased cellular stress on the remaining podocytes resulting in glomerular sclerosis if podocyte loss exceeds the threshold of 20%. Therefore it is of utmost importance to understand the beneficial and deleterious aspects of cytoskeletal stress and rearrangements in podocytes to identify new therapeutic approaches. Hence, our research proposal aims to analyze the interplay of cytoskeletal reorganisation, the resulting tension on the actin cytoskeleton and the effects on intracellular calcium levels in real time in the murine kidney in vivo. Therefore, we will employ a multi-layered state-of-the-art imaging approach including intravital multiphoton microscopy, innovative reporter mouse models, serial multiphoton imaging and superresolution technologies. The overarching goal of this research proposal is to characterize cytoskeletal rearrangements in podocyte hypertrophy in response to podocyte damage at early stages of FSGS and match this with intracellular Ca2+ signaling.