Project description
Targeting a novel mechanism in drug-resistant pathogens
Pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa represent major therapeutic challenges, as they can develop multidrug resistance. Antimicrobial resistance has escalated as a global health threat, necessitating the development of new antibiotics against novel, conserved bacterial processes crucial for survival but unaffected by resistance mechanisms. Funded by the Marie Skłodowska-Curie Actions programme, the TRANSPEPTID project focuses on trans-translation, a vital biological process found in bacteria that releases stalled ribosomes during protein synthesis. Researchers will engineer antimicrobial peptides to disrupt protein synthesis in resistant pathogens, offering new solutions in the face of antimicrobial resistance.
Objective
Antimicrobial resistance (AMR) poses a major threat to human health around the world. The AMR crisis has emerged as one of the leading public health threats of the 21st century. This global crisis is due to the fact that bacteria share and increasingly develop new resistance mechanisms as a consequence of the misuse of antibiotics, as well as a lack of new drug development. To combat this crisis, we need new classes of antibiotics, and most importantly, against new targets. It is therefore crucial to identify new molecular processes that can be targeted. Ideally, these should be: i) conserved among all pathogenic ESKAPE bacteria; ii) indispensable to bacterial survival or at least its fitness; iii) sufficiently variable that different species can be distinguished from each other; iv) absent in eukaryotes; v) not targeted by current antibiotics; vi) unrelated to existing AMR mechanisms; and finally, vii) reproducible in non- hazardous in vitro experiments. In this quest, trans-translation appears to be a perfect candidate. Development of new antibiotics that target trans-translation from multidrug resistant ESKAPE pathogens will be addressed in this project (TRANSPEPTID). We will use engineer antimicrobial peptides based on the C- terminal tails of SmpB proteins from ESPAKE pathogens with the propose to compete with endogenous SmpB, and in turn to inhibit trans-translation. The project is organized in three main objectives that will constitute three major breakthroughs in the field: (OB1) Optimization and characterization of designed peptides in ESKAPE pathogens, (OB2) Biophysical analysis of selected peptides in target ESKAPE pathogens, and (OB3) Determination of the high- resolution structures of the complexes between the peptides and their molecular targets by cryo-EM. Since TRANSPEPTID is a multidisciplinay project that embraces both fundamental and applied science, it will contribute significantly to strength the research and training profile of the researcher
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 biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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35042 Rennes
France
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