Objective
Directed evolution (DE) is a uniquely powerful approach for mapping sequence to function and engineering potent biomolecules. Yet despite transforming diverse fields, DE has never been applied to the most numerous class of human genes: long non-coding RNAs (lncRNAs). LncRNA research is stalled at the ‘sequence-function gap’. Until we can connect sequence to cellular phenotype, lncRNAs’ biology will remain opaque and their therapeutic potential untapped.
To break this barrier, I will pioneer the directed evolution of lncRNAs by developing DELFIN - the first technology platform for continuous, multi-cycle evolution of lncRNAs in their native cellular context. DELFIN will deliver experimental fitness landscapes for lncRNAs and ‘Enhanced lncRNAs’ with potent bioactivity. These will allow us to study lncRNAs’ evolutionary principles, connect them to underlying molecular mechanisms, and train predictive models for de novo design. DELFIN is inherently scalable to hundreds of lncRNAs in parallel. Its feasibility is underpinned by extensive preliminary data, which has already de-risked the core methodological innovations.
As a proof of concept for its translational applications, I will apply DELFIN to the urgent unmet medical need of liver disease, evolving hepatoprotective Enhanced lncRNAs and confirming their therapeutic efficacy in clinically-relevant disease models.
REVOLVER offers a dual breakthrough. First, it will deliver the first ever sequence-function maps for this major class of human genes, transforming our fundamental understanding. Second, it will establish a powerful yet practical platform, applicable across the widest range of RNA types and biological contexts, to systematically decode and engineer functional RNAs. REVOLVER will finally crack the design principles of lncRNAs, establishing an evolution-driven paradigm to explore the non-coding genome and engineer a new generation of RNA medicines.
Fields of science (EuroSciVoc)
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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)
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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-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.
4 Dublin
Ireland
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.