Project Details
Projekt
Modulation of the podocyte actin network
Subject Area
Nephrology
Term
since 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 241702976
Foot process effacement is a characteristic morphological feature of podocyte injury and reflects structural changes in the podocyte actin cytoskeleton. These changes are accompanied by cytoskeletal rearrangements and a hypercontractile actomyosin machinery, leading to dysfunction of the glomerular filtration barrier. Podocytes, which play a crucial role in the kidney’s filtration function, may lose their ability to maintain the glomerular barrier due to this damage, resulting in proteinuria and progressive kidney failure. However, it remains unclear whether these restructuring processes exhibit specific patterns in different glomerular diseases and how they correlate with the severity of podocyte injury. Various glomerular diseases, such as Minimal Change Disease, focal segmental glomerulosclerosis, or membranous nephropathy, are associated with distinct mechanisms of podocyte injury that may differ in the way foot process effacement and cytoskeletal rearrangements occur. The aim of this project is to gain a comprehensive understanding of podocyte cytoskeletal dynamics in health and disease. Through integrative network analyses and in situ detection methods, we seek to identify both universal and disease-specific signatures that trigger the uniform restructuring of the actin cytoskeleton (manifested as foot process effacement). A specific antibody panel (Core Podocyte Cytoskeleton Signature, CPCS) and cyclic multiplex immunofluorescence microscopy will be used to annotate glomerular injury patterns in animal models and biopsies and correlate them with clinical parameters. Additionally, key regulators of the mechanobiological balance will be functionally analyzed to develop pharmacological modulation strategies and innovative therapeutic approaches for glomerular diseases.
DFG Programme
Research Grants
