Project description
Introducing supramolecular self-replicating antimicrobials
Antimicrobials are essential to treat and cure disease and infection. However, the high mutation rates of microbes and their capacity to develop resistance pose a threat to the effectiveness of many existing antimicrobials. This calls for the development of new antimicrobial agents with novel mechanisms. The ERC-funded Replicate project aims to design a new family of supramolecular self-replicating antimicrobials as an alternative to widely used single-molecule drugs. Specific metabolic routes of bacteria will transport dormant supramolecular precursors into the bacterial membrane where they will band together to create self-assembling peptide amphiphiles. Once established, the assemblies can catalyse their own synthesis, or self-replicate, thus accelerating production of peptide amphiphiles to increase membrane damage in target pathogens.
Objective
This project aims to address the urgent need for new antimicrobial agents by developing a conceptually new strategy to damage bacterial membranes with supramolecular fibres.
Dormant (non-assembling) precursors will accumulate in the membrane of bacteria for in situ switch-on of self-assembly and membrane lysis. Specific metabolic routes of bacteria, absent in mammalian cells, will be used to transport supramolecular precursors into the membrane of bacteria with full cell specificity. Once in the membrane, precursors will combine to generate self-assembling peptide amphiphiles (PAs).
Importantly, once formed, the supramolecular assemblies can catalyse their own synthesis in bacterial membranes, causing a dramatic acceleration in PA production and antimicrobial fibrillation. This unprecedented antimicrobial design borrows concepts from cooperative self-assembly, supramolecular autocatalysis and rational peptide design, leading to a self-amplified therapeutic action.
This will be the first self-replicating antimicrobial that can make copies of itself to boost membrane damage once activated in target pathogens. Co-assembly of PAs and their precursors will create catalytic microenvironments by templation of reactive building blocks.
Overall, this project will lay down structural and mechanistic determinants for biological membrane interfacing with targeted and self-replicating supramolecular nanomaterials.
In a broader picture, the REPLICATE technology aims to spark a re-conceptualisation of drug design by drawing the attention to supramolecular therapeutics, which may open new exciting opportunities in biomedicine not accessible from traditional single-molecule drugs.
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 biochemistry biomolecules
- engineering and technology nanotechnology nano-materials
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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-2024-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.
15782 Santiago De Compostela
Spain
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.