Single cell resolution of human chronic kidney disease for precision medicine in nephrology

• Applicants: Professor Dr. Rafael Kramann; Professor Dr.-Ing. Julio Saez-Rodriguez; Professor Dr. Oliver Stegle, Ph.D.
• Subject Area: Nephrology
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433151787

Chronic kidney disease (CKD) affects more than 10% of the German population but lacks targeted therapies as well as precise prognostic tools. We have access to a unique biobank of human kidney biopsies with extensive clinical follow up data of up to 10 years. We are aiming to characterize 10 kidney diseases (common and rare) contributing to a majority of CKD by using single nuclear snRNA-seq and snATACseq from frozen human kidney biopsies. Living kidney donor biopsies will serve as healthy controls. We are aiming for 200 biopsies (20 per kidney disease type) with a minimum of 5 year follow up data. Among the 20 biopsies up to 10 will be included with stable kidney function during follow up and 10 with significant decline of kidney function. We will deploy new strategies for pooling patient samples and demultiplexing the data based on SNP analysis, as well as functional genomics methods tailored to single cell data to extract information about deregulated pathways, transcription factors and other processes, to identify novel biomarkers and therapeutic targets. This ambitious interdisciplinary project requires the expertise of nephrologists, computational and molecular biologists, and machine learners. It will only be possible by leveraging the resources at the DFG sequencing centers. The passion that drives this project results from a simple hypothesis: It is possible to find novel urgently needed therapeutic targets and prognostic measures for CKD using state of the art single cells genomics.

• DFG Programme: Research Grants