Project description
Metabolic control in kidney repair
The tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, is a central metabolic pathway that generates energy from carbohydrates, fats, and proteins. Emerging evidence links this pathway with failed kidney repair and fibrosis due to lack of metabolic intermediates that are crucial for chromatin remodeling and cell signalling. The ERC-funded SPARK project aims to explore how disrupted cell metabolism and metabolic interactions within the kidney microenvironment affect injury and repair. Researchers will undertake multiomics analysis to identify and validate in vitro and in vivo potential molecular targets. This research will advance understanding of metabolic control in kidney repair and tissue homeostasis.
Objective
Chronic kidney disease (CKD) is a global health concern, and the limited treatment options for end-stage kidney disease have remained unchanged for decades. Concurrent insults to the kidney can exacerbate disease progression, but the underlying potential to have kidney repair after such injury remains poorly understood. The tricarboxylic acid (TCA) cycle, a fundamental metabolic pathway, plays a vital role in energy production and biomolecule synthesis. Recent research by my group has revealed that failed repair and subsequent fibrosis in kidney epithelial cells are linked to anaplerotic failure in the TCA cycle, resulting in the inability to maintain sufficient levels of TCA intermediates. These metabolites regulate chromatin remodeling and cell signaling pathways, influencing cell fate decisions. SPARK aims to investigate the impact of perturbed cell metabolism and metabolic crosstalk within kidney microenvironments on cell fate decisions during injury and repair. The project will map the metabolic, proteomic, and transcriptomic interactome at an unprecedented resolution, focusing on the kidney tissue microenvironment. By integrating spatial multi-omics data, exometabolite interactome analysis, and human kidney biopsies, actionable targets will be identified. In vivo studies using reporter mice and ex vivo preserved human kidneys will validate the metabolic effects of the selected targets. This research will provide insights into how the metabolic interactome governs repair through epigenetic modulations in the kidney and establish a paradigm for studying tissue homeostasis in various contexts.
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.
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.
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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.1.1 - European Research Council (ERC)
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Topic(s)
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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
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.
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-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
2333 ZA Leiden
Netherlands
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