Project description
Peptides that disrupt bacterial membranes
Antibiotic resistance occurs when bacteria evolve mechanisms to avoid being killed by one or multiple antibiotics. It poses a significant medical threat as it renders antibiotics ineffective, necessitating the development of novel treatments. The aim of the EU-funded PeptideKillers project is to design and test promising peptide therapeutics that are selective for bacteria and leave human cells unaffected. Researchers will model bacterial membranes and test various peptides for their ability to form pores and cause membrane disruption. PeptideKillers will lead to promising peptides with antimicrobial activity and offer the technology to expand membrane-targeting peptides against other pathogens or cells.
Objective
Antibiotic-resistant bacteria cause more than 700 000 deaths per year, and the forecast is 10 million per year in 2050. Moreover, emerging strains of bacteria resistant to all available antibiotics may lead to a global post-antibiotic era. Because of this threat, the WHO and the UN are encouraging the research and development of new treatments. The aim of this proposal is to design new peptides that selectively target and disrupt the membranes of pathogens but not those of human cells. To obtain such peptides, we will develop an innovative coarse-grained model of membranes and an original growth method, which will enable us to establish the relationship between peptide sequence motifs and their affinity to membranes with specific lipid compositions. Moreover, we will determine the critical peptide properties required for membrane disruption via the formation of transmembrane pores and spontaneous peptide translocation across membranes by devising new collective variables capturing these processes. Our computational advances will be complemented by experimental verification from peptide-membrane affinity measurements plus leakage and flip-flop fluorescence assays assessing membrane disruption. The most effective peptides will be evaluated for antimicrobial activity and human cell toxicity using growth inhibition and hemolytic assays, respectively. We will investigate mixtures of peptides for their synergistic increase in antimicrobial activity, and we will uncover the molecular mechanism of their synergism. The peptide behaviour will be quantified under equilibrium and more biologically relevant non-equilibrium conditions. The methods and knowledge obtained within this project will not only enable us to determine new peptides selectively killing bacteria, but will also enable the development of peptides targeted against membranes of enveloped viruses, cancer cells, or even cellular organelles with potential application as sensors, biomarkers, or therapeutics.
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 microbiology virology
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences clinical medicine oncology
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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.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2020-COG
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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.
601 77 Brno
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.