Objective
Ribosomes have the potential to polymerize many types of building blocks beyond the L-alpha amino acids we observe in nature. However, the evolution of essential genes towards new or enhanced activities is often confounded by interactions with host machinery. A long-standing aim of the ribosome engineering field is the complete decoupling of ribosome function from the host, freeing a population of ribosomes within a live cell for researchers to modify, engineer, or evolve towards new polymerization chemistries. Previous attempts to decouple or “orthogonalize” ribosome sub-populations have come through the creation of orthogonal 16S ribosomal RNA – messenger RNA pairs. Unfortunately, this does not orthogonalize the ribosome large subunit where polymerization occurs. Here, we propose a path towards an organism with two mutually orthogonal genetic decoding systems (specialized ribosomes), creating two discrete ribosome–transfer RNA (tRNA) subpopulations, and freeing a population of ribosomes to evolve for new functions. We aim to decouple the large ribosomal subunit by engineering the universal ribosome–tRNA tail interaction. To achieve this, we will investigate the expression of tRNAs bearing non-CCA 3’ ends in live cells (WP1). We will test the aminoacylation of non-CCA-end tRNAs by natural and engineered aminoacyl-tRNA synthetases (WP2). Finally, we will develop a platform for directed evolution of the ribosome large subunit rRNA (WP3). Achieving complete ribosome–tRNA pool orthogonalization will generate new knowledge in basic ribosome biology and open the potential for DNA-encoded synthesis of biopolymers with new sidechain and backbone chemistries for drug discovery and biomanufacturing. The far-reaching implications go beyond biopolymer synthesis and microbial-based manufacturing to complement biocontainment strategies in the emerging field of genome writing.
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 drug discovery
- natural sciences biological sciences genetics RNA
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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-2026-STG
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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.
A94 X099 BLACKROCK 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.