Objective
Chronic inflammation underlies autoimmune diseases, cancer, and aging. Yet current therapies fail to address underlying metabolic dysregulation of one-carbon metabolism (1C) or unresolved DNA damage triggering oxidative DNA damage response (OxDDR) that fuel persistent immune activation cycles. Here, we want to decode and target the one-carbon metabolism–oxidative DNA damage response (1C–OxDDR) axis, a critical but underexplored driver of persistent immune activation. We hypothesize that chronic DNA damage and rewired 1C metabolism enforce stable, disease-promoting immune phenotypes. To test this, we will map 1C–OxDDR circuits in patient tissues and aging models using multi-omics, spatial transcriptomics, and metabolic flux profiling to define signatures of disease initiation, progression, and therapy resistance. We will identify novel disease drivers and develop precision small molecules, leveraging our track record in developing first-in-class inhibitors to MTHFD1&2, OGG1 and MTH1 using an AI-integrated drug design. Furthermore, we will pioneer catalytic medicine through OGG1 amplizymes, introducing a new therapeutic paradigm that introduces novel enzymatic functions to proteins rather than inhibiting them. These strategies will be validated in advanced preclinical systems, including organoids and humanized models to reprogram immune dysfunction without broad immunosuppression. This high-risk/high-gain program builds on our success in synthetic lethality and PARP inhibitors, aiming to deliver a new precision medicine platform for inflammation-driven diseases. By integrating mechanistic insight with innovative medicinal chemistry, RECODE seeks to break the vicious cycle of chronic inflammation, opening therapeutic opportunities across auto-immunity, cancer, and aging, with impact comparable to our previously discovered paradigm-shifting cancer therapies.
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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)
MAIN PROGRAMME
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Topic(s)
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.
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-2025-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.
171 77 STOCKHOLM
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.