Project description
Towards a new antimicrobial strategy: targeting secondary DNA structures in bacteria
The G-quadruplex (G4) DNA, a secondary structure of DNA seen in both eukaryotic and prokaryotic cells, has been associated with important biological processes. In Pseudomonas aeruginosa, a highly pathogenic bacterium responsible for hospital-acquired infections, G4 DNA forms at the gene promoters, and disruption of these structures kills bacteria. The EU-funded G4-AntiBac project will investigate the function of G4 DNA in bacteria and develop novel compounds that target these secondary structures as an antimicrobial strategy. The project addresses the need for the identification of novel bio-molecular targets for the development of new classes of antibiotics, helping to combat antimicrobial resistance.
Objective
There is a pressing need to develop new antimicrobial approaches to combat bacterial resistance to antibiotics. Pseudomonas aeruginosa – a dreadful Gram-negative bacterium pathogen associated with severe acute and chronic human diseases – is responsible for 10-15 % of hospital-acquired infections worldwide. Thus, it is important to identify new biomolecular targets in bacteria and design new molecules that can selectively target them. This project aims to study G-quadruplex DNA (G4 DNA) structures as a new bio-molecular target for the development of new classes of antibiotics. G4 DNA is a non-canonical structure of DNA whose formation has been associated to a number of important biological processes. While the function of G4 DNA is well established in eukaryotic cells, far less is known about their functions in bacteria. Preliminary data from the host group has shown that G4 DNA’s can form in gene promoter regions of the genome in P. aeruginosa. They have also shown that metal complexes can bind to this G4 DNA regions and display antibacterial activity. In this project, I propose to develop novel compounds (via a ‘target-guided synthesis’ approach) that can specifically bind with high affinity to G4 DNA structures of relevance to bacteria. If the newly developed bacterial G4 DNA binders exhibit low cellular uptake, I propose to implement the well-established liposomal delivery strategies to improve their uptake into the targeted bacterial strains. Finally, the highly active compounds will be used to study the proposed gene regulatory role that G-quadruplexes play in P. aeruginosa. My proposed research falls under one of the key priorities (i.e. Infectious diseases and improving global health) of the Horizon-2020 work programme. The outcome of the proposed study will have impact in addressing one of the key objectives (i.e. Develop New Therapeutics and Alternatives) of the recently documented ‘European One Health Action Plan against Antimicrobial Resistance’.
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 microbiology bacteriology
- natural sciences biological sciences genetics DNA
- medical and health sciences health sciences infectious diseases
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
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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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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.
SW7 2AZ London
United Kingdom
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.