Project description
The next generation of antimicrobial drugs
Antimicrobial resistance is a growing health concern hampering the effectiveness of existing antibiotics. The emergence of drug-resistant pathogenic bacteria demands the development of novel antimicrobial solutions. To address this, the EU-funded AmCaLiStat project will develop drugs that target Lipid A, the component that anchors LPS to Gram-negative bacterial membranes. The idea is to disrupt lipid assemblies paramount for membrane integrity and pathogen survival. Using specialised statistical software, scientists will uncover correlations between the structure and activity of drugs against Lipid A, leading to the modular synthetic design of promising new antimicrobials. Apart from novel drugs, this approach could potentiate obsolete antimicrobials.
Objective
"Antimicrobial resistance in bacteria is a growing public health crisis, as common drugs are becoming ineffective against many species of pathogenic bacteria. This research aims to devise highly specific and stable antimicrobials, which target the amphiphilic component that anchors LPS to Gram-negative bacterial membranes, “Lipid A”, for direct antimicrobial effect and to potentiate other antimicrobials. Taking inspiration from bacterial lipids, which possess multiple tails and a polybasic headgroup, synthetic cationic lipidoids have the potential to be highly specific bacterial membrane-targeting antimicrobials. Preliminary results demonstrate that some cationic lipidoids bind and disrupt bacterial lipid assemblies, and significantly inhibit the growth of E. coli at micromolar concentrations. However, the breadth of potential molecular structures arising from the range of available starting materials makes the search for optimum compounds an insurmountable task. This proposal outlines an innovative use of statistical software to steer modular synthetic design and expedite the identification of promising new antimicrobials. Relative to a ""one-factor-at-a-time"" approach, statistical design can quickly uncover correlations between structure and activity, and unexpected interactions between structural variables, thus accelerating the discovery of antimicrobial compounds that would not otherwise be obvious. In addition to uncovering new compounds selective to bacteria, libraries of lipidoids will be investigated to help uncover design rules for the effect of shape on membrane interactions, and generic mechanisms of membrane-targeting antimicrobial action. Results could also lead to new means to potentiate obsolete antimicrobials that are impermeable to bacterial membranes, or act as a chaperone for highly effective but relatively unstable antimicrobial peptides."
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 computer and information sciences software
- medical and health sciences health sciences public health
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
8010 GRAZ
Austria
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.