Project description
Plasmids and antibiotic resistance spread
Bacteria have evolved sophisticated defence mechanisms to fight invading viruses. Plasmids – small DNA molecules that carry and spread antibiotic resistance genes between bacteria – must equally evade these defence systems during transfer. However, the underlying mechanisms remain poorly understood. The ERC-funded DEFCONJ project focuses on anti-defence elements on plasmids themselves that become activated during transfer. Researchers will use machine learning, structural analyses and functional experiments to characterise these systems and determine how they collectively neutralise bacterial defences. Project findings will advance our understanding of antibiotic resistance dissemination and enable the design of new tools for synthetic biology and clinical applications.
Objective
The microbial world's genomic arms race spurred a remarkable diversity of defense and anti-defense mechanisms, with CRISPR-Cas and anti-CRISPR systems as prime examples that revolutionized genome editing. Recent years have seen a surge in the discovery of bacterial anti-phage systems and their viral countermeasures, yet little is known about how plasmids—key vectors of antibiotic resistance—overcome host defenses. Our lab recently found that plasmids' leading regions, the first to enter recipient cells, harbor diverse anti-defense systems vital for efficient conjugation. This sets the stage for in-depth studies of plasmid-encoded anti-defenses (PEADs), significantly advancing our understanding of conjugation, with far-reaching implications for clinical and biotechnological applications.
Here, we will explore PEADs through three interconnected aims. In Aim 1 we will develop machine-learning and language model approaches, complemented by structural analyses, to identify and characterize putative PEADs from extensive genomic and metagenomic databases. This will be followed by functional testing in both targeted and high-throughput assays. In Aim 2 we will elucidate PEAD regulation, including early expression from single-stranded promoters and unique mechanisms for transient expression, integrating state-of-the-art computational approaches with in vitro transcription and conjugation efficiency assays. In Aim 3 we will determine how multiple PEADs function in concert to counteract multilayered defenses, informing the design of tailored plasmid-leading regions for efficient DNA transfer to targeted bacteria. DEFCONJ tackles a fundamental question: how do plasmids achieve efficient conjugation despite host defenses? Beyond transforming our understanding of the plasmid-host arms race, this research will advance our comprehension of antimicrobial resistance dissemination, while paving the way for powerful new tools for clinical and synthetic biology applications.
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 databases
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics genomes
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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)
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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.
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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.
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Call for proposal
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(opens in new window) ERC-2025-COG
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69978 Tel Aviv
Israel
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