Project Details
Projekt
Dissecting regulatory programs of kidney disease transition using functional genomics
Subject Area
Nephrology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445703531
The kidney is one of the most heterogeneous organs with over 26 cell types. We hypothesize that distinct cell-specific programs (regulated by transcription factors) govern the transition of glomerular diseases and acute kidney injury (AKI) to chronic kidney disease (CKD) and the response to therapeutics such as the glucocorticoids. We will use single cell sequencing technologies to dissect transcriptional (scRNA-seq) and regulatory programs (snATAC-seq) at unprecedented throughput and depth targeting tens of thousands of kidney cells. These complementary techniques will allow us to analyze transcriptional and epigenetic changes and provide a finer characterization of transition and reprogramming states of cells. As the basis for this application, we have established the full pipeline for scRNA and scATAC-seq for human and mouse fresh frozen kidney tissues (Kuppe in cooperation with Kramann). This includes a novel plate based scATAC-seq protocol, which allows a cost-effective measurement of open chromatin regions of pre-sorted nuclei or cells. The molecular and clinical genomics expertise from Kuppe will be complement by the computational expertise of Costa, who established computational pipelines for analysis of scRNA-seq or snATAC-seq to investigate cellular changes during diseases. In conclusion, within this application, we aim to use state-of-the-art functional genomics approaches to unravel the complex cellular and molecular heterogeneity of disease transition in experimental mouse models and human kidney diseases (Alport disease and focal segmental glomerulosclerosis, FSGS). Our data will characterize affected cell-specific regulatory pathways and might lead to the identification and validation of novel diagnostic approaches and also therapeutic targets.
DFG Programme
Clinical Research Units
