Project description
Metabolic reprogramming and chronic kidney disease
Chronic kidney disease (CKD) is associated with progressive and irreversible loss of kidney function, which ultimately leads to renal failure and end-stage kidney disease. One of the hallmarks of CKD is fibrosis, which stems from the accumulation of extracellular matrix (ECM) components upon irregular activation of myofibroblasts. Funded by the Marie Skłodowska-Curie Actions programme, the MetaboKID project focuses on the role of cellular metabolism during fibrosis. Researchers will investigate how metabolic rewiring in myofibroblasts influences fibrosis and CKD. Using advanced multi-omics, computational analyses, and innovative in vitro systems, the research seeks to develop metabolism-based therapies for CKD.
Objective
Chronic kidney disease (CKD) affects 10% of the population and fibrosis driven by excessive accumulation of extracellular matrix (ECM) is the hallmark of CKD. Myofibroblasts are the key ECM producing cells and are activated by cross-talk with injured proximal tubule anChronic kidney disease (CKD) affects 10% of the population and fibrosis driven by excessive accumulation of extracellular matrix (ECM) is the hallmark of CKD. Myofibroblasts are the key ECM producing cells and are activated by cross-talk with injured proximal tubule and immune cells. Although a derangement in fatty acid oxidation (FAO) of tubular epithelium is crucial in the pathophysiology of CKD, the metabolic rewiring of kidney myofibroblasts remains elusive. Our preliminary observations suggest that cell type-specific metabolic shifts could define new cellular subpopulations with a differential role in the fibrogenic response. To understand this, the following objectives have been defined: 1. To decipher the role of FAO in myofibroblasts during kidney fibrosis; 2.To dissect metabolic changes as important drivers of kidney fibrosis and CKD; 3. To validate key metabolic pathways in complex ex vivo models of kidney fibrosis. To address these aims, I will map the genetic and metabolic spatio-temporal features of kidney fibrosis by a combination of cutting-edge multi-omics technologies at large scale (Spatial single cell ATAC sequencing for transcriptomics and Space M for metabolomics). This will be complemented by advanced computational analyses and modeling, using CKD human biopsies and mouse renal samples from available genetic models for myofibroblast tracing and FAO enhancement. Innovative in vitro systems (cell coculture and kidney organoid systems) will be used to identify and target cell type-specific metabolic reprogramming. Strategies based on the modulation of these metabolic shifts will provide a firm basis for novel, metabolism-oriented therapeutic approaches against renal fibrosis and CKD.
Fields of science (EuroSciVoc)
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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.
- medical and health sciences basic medicine physiology pathophysiology
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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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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52074 Aachen
Germany
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