Many genes mutated in kidney diseases encode for solute carrier proteins. The concentrations of substrates transported by these transport proteins therefore represent biomarkers of protein function. Genome-wide genetic screens have the potential to discover previously unknown transporter – substrate relationships, yielding a wealth of novel functions for putative CKD risk genes. The objective of the PhD project is, based on transporter – substrate associations identified in genome-wide genetic screens in a large CKD patient cohort – to translate these relationships into mechanistic insights. Their experimental validation will establish the necessary insights into the function of novel therapeutic targets to treat kidney diseases. The goals of the PhD project are to i) validate the statistically established gene function using a combination of molecular biology and state-of-the-art membrane transport studies, and to ii) establish the causal mutations using a combination of genome-editing, imaging and transport studies.
- Newly genetic determinants of non-traditional markers of CKD progression and their association kidney failure and across CKD subtypes;
- Prioritization of the most likely genes and variants underlying the genetic associations as the basis for experimental validation in other ESR projects;
- Insights into causality of non-traditional biomarkers for CKD progression to inform follow up by pharma partners;
- Generation of a genome-wide interrogation resources for genes emerging from other ESR projects.