Prof. Thomas Benzing

Nephrolab Cologne

University Hospital of Cologne Kerpener Str. 62
Gebäude: 15
Zimmer: 1st floor
50937 Cologne

Project proposal:

Our lab is interested in the molecular events that contribute to progressive kidney disease. The focus of our research is on two classes of disorders, glomerular diseases and renal cystic kidney disease. Using conventional and conditional loss-of-function mutations in mice, the model organisms C. elegans and Drosophila melanogaster in combination with biochemistry, proteomics and human genetics the lab has contributed to an entirely new understanding of these important groups of disorders.

This research project focuses on podocyte biology and glomerular disease. The podocyte is one out of three main cell types that make up the glomerulus, a collection of small blood vessels that form the filtration barrier of the kidney. Podocytes are fascinating cells with a unique morphology. With hundreds of foot processes podocytes are interconnected and cover the entire outer surface of the capillary lumens within the glomerulus. They act as highly dynamic pericytes of the glomerular capillaries, and genetic studies revealed their essential role for the integrity of the glomerular filtration barrier. This filter has astonishing properties - while producing approximately 180 liters of primary urine a day the kidney filter retains almost all proteins in the blood. Our work pioneered the concept that signalling at a specialized cell contact called slit diaphragm of podocytes is essential for developing and maintaining this kidney filtration barrier.

The proposed PhD project we will clarify the role of miRNAs in the development and biology of podocytes. Regulation of gene expression through miRNAs presents an evolutionary highly conserved mechanism crucial for the development and maintenance of many tissues. miRNAs have been shown to be involved in the pathogenesis of several diseases, the number of which is still increasing. Recent data from our lab underlines the importance of miRNAs in the kidney: Knockout of DICER in both, epithelial cells of the kidney tubules and podocytes results in severe changes of kidney morphology and function and in the development of endstage renal disease. This PhD project follows 3 overarching goals: (1) we want to confirm and validate the clinical data and miRNA profiles from the DICER models by using DGCR8 knockout mice, another model of complete miRNA depletion, (2) we aim to identify individual miRNA-mRNA pairs essential for podocyte survival and function in silico by integrating mRNA and miRNA expression profiles including existing profiling data from kidney development and in vivo by using the PAR-CLIP technique, and (3) we want to clarify the role of single miRNAs (“podoMirs”) in vivo in mouse models, C. elegans and human glomerular disease

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