Project description
Kidney organoids with genetic mutations shed light on renal fibrosis mechanisms
Renal fibrosis – the progressive scarring of kidney tissue – is the final stage of chronic kidney disease, often leading to kidney failure, and its mechanisms remain poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the DeSiFRO project aims to use nephronophthisis, the most common cause of kidney transplantation in children, to shed light on renal fibrosis mechanisms. Nephronophthisis is caused by dysfunction of cilia on renal epithelial cells that are essential sensory antennae for cellular signalling. DeSiFRO will use genetically mutated kidney organoids to investigate potential defective signalling underlying renal fibrosis in nephronophthisis. Insights could point to drug targets for nephronophthisis and chronic kidney disease.
Objective
Chronic kidney disease (CKD) affects up to 10% of the world population and is characterized by decreased renal filtration and scarring (fibrosis). However, the mechanisms underlying renal fibrosis remain largely unclear, which hampers drug development. In this research, I will elucidate mechanisms underlying renal fibrosis using state-of-the-art techniques, like live fluorescence microscopy and single-cell RNA sequencing (scRNAseq), to analyze human renal organoids. I will focus on a genetic fibrotic kidney disease called nephronophthisis (NPHP), which is the most common cause for kidney transplantation in children. NPHP is a ciliopathy, caused by primary cilia dysfunction. Primary cilia are crucial antennae for cellular signalling and hence I hypothesize that defective signalling is underlying renal fibrosis development in NPHP. I will use kidney organoids with genetic mutations as in vitro models to elucidate the affected signalling pathways. First, I will characterize the effect of mutation severity on the ciliary and fibrotic phenotype using immunofluorescence. Then, I will identify the origin of collagen-producing cells using fluorescent reporter-cells and scRNAseq. I will also use the scRNAseq data to identify disturbed signalling pathways in both renal tubular and stromal cells. Lastly, I will evaluate signalling dynamics of the disturbed pathways by live imaging of biosensors in wildtype and mutant organoids. This research will produce a comprehensive overview of signalling mechanisms underlying renal fibrosis in ciliopathies, which could aid the identification of novel drug targets for NPHP, or other forms of CKD. Performing this research will allow me to expand my expertise in advanced analysis of human in vitro models. This will bring me to the forefront of the cell biology field and together with the development of transferable skills, like leadership and strategic communication, this will prepare me for a career in a leading position in the field.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine nephrology kidney diseases
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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8006 Zurich
Switzerland
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