Objective
An accumulating body of evidence reveals that the Genetic Code, canonically interpreted in codons of three nucleotides, is not universal. In dogma challenging findings, we have observed in unicellular protists a remarkable malleability of genetic decoding that is mostly governed by tRNAs that interpret codons as having different meanings depending on their location in the genome. For example, coding sequences of our model protist Blastocrithidia nonstop are rich in stop codons and unique tRNA architectures are employed to readthrough them efficiently. Importantly, these internal stops very much resemble premature termination codons (PTC) in humans that lead to truncated proteins and are the cause of ~11% of human genetic disease. As such, these small RNA molecules with innate readthrough properties hold tremendous promise for the treatment of disease.
Our first objective is to explore and characterize the molecular mechanisms of alternative genetic decoding in protists where this phenomenon is most prominent. Armed with this knowledge, our second objective is to engineer tRNAs and tRNA-specific readthrough-inducing drugs (TRIDs) for programmable alterations of genetic decoding in heterologous systems. tRNAs and TRID will then be applied in cellular and animal models of severe monogenic paediatric diseases.
We have assembled a team that synergizes expertise across disciplines. JL is a leading protist biologist, LV specializes on translational control, ON in engineering stop codon readthrough drugs, and MO in clinical disease models. This intertwined collaboration of all four PIs will expedite the characterization of alternative decoding mechanisms and their ultimate application in cellular and in vivo models of human diseases. Successful completion of 3Stops2Go is only possible by close teamwork and aims to deliver a new class of tRNA molecules and readthrough pharmaceuticals that will be a paradigm shift in basic science with direct and broad therapeutic potential.
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.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics nucleotides
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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-SYG - HORIZON ERC Synergy Grants
See all projects funded under this funding scheme
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-SyG
See all projects funded under this callHost institution
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.
142 00 PRAHA 4
Czechia
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.