Objective
Current models present an increasingly complex picture of mRNA translation, in which several pathways work together to define protein output in a context-dependent way. Disruptions can lead to disease, yet we are only beginning to crack the combinatorial code that links mRNA features to correct translation levels. Yet, translation is characterized by a confined and modular cis-regulatory space, making it ideal for dissecting function with cutting edge genomics and machine learning (ML).
TRANS-DECODE will deliver a systematic, data- and model-driven strategy for decoding the regulation of mRNA translation at unprecedented resolution and interpretability. Our innovative approach will combine high-throughput massively parallel reporter assays (MPRAs), ribosome profiling, and CRISPR based validation screens with explainable AI and RNA foundation models. We will use iterative design-build-test cycles in human cells and zebrafish as vertebrate model to construct interpretable, predictive models of translation initiation, elongation, and mRNA stability. The project is structured into four ambitious and synergistic aims:
1. Determine the RNA sequence/structure determinants of translation initiation in 5’UTRs using MPRAs and interpretable ML.
2. Connect sequence features to regulatory pathways by perturbing translation initiation factors.
3. Dissect spatial-temporal translation control in vertebrates by adapting MPRAs to spatial single-cell resolution in zebrafish development.
4. Develop generative models of translation that encompass initiation, elongation, and RNA stability to identify pathogenic sequence variants.
The insights gained will not only unravel the molecular logic of translation and open new paths to correct non-coding mutations in human disease, but also enable a directed design of RNA for therapeutic and synthetic biology applications. This will position the project as a blueprint for an AI-driven systematic dissection of cis-regulatory mechanisms.
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.
- natural sciences biological sciences synthetic biology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences computer and information sciences artificial intelligence generative artificial intelligence
- natural sciences biological sciences genetics RNA
- natural sciences computer and information sciences artificial intelligence machine learning
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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.
13125 Berlin
Germany
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.