Project description
Mapping drug-membrane battles to fight superbugs
Multidrug-resistant bacteria threaten millions of lives. While lipid-targeting antibiotics such as daptomycin offer a vital line of defence, their molecular killing mechanism remains largely a mystery. The ERC-funded STAR project aims to solve this by using solid-state NMR spectroscopy to visualise atomic-level battles between drugs and bacterial membranes. It will develop specialised labelled phospholipids and boost sensor sensitivity so that researchers can observe how antibiotics lock onto and disrupt complex cell walls. These insights allow scientists to identify structural weaknesses in superbugs and provide a roadmap for designing more potent, safer treatments. The project’s goal is to recreate the antibiotic pipeline through precision molecular engineering.
Objective
Antimicrobial resistance (AMR) is escalating due to multidrug-resistant (MDR) bacteria and a dwindling antibiotic pipeline and is projected to cause up to 10 million deaths annually by 2050. Lipid-targeting (LT) antibiotics such as daptomycin and polymyxins combat MDR infections by disrupting bacterial membranes, yet their mechanisms remain unclear due to major technical challenges for structural biology. This knowledge gap hinders the development of next-generation LT-antibiotics with improved efficacy and safety profiles.
STAR will positively impact structural biology capabilities by channeling the potential of Solid-State Nuclear Magnetic Resonance (ssNMR) spectroscopy to provide atomic-level insights into LT-antibiotic interactions under physiologically relevant conditions. By optimizing the scaled production of pure, 13C/15N-labeled phospholipids, STAR will overcome key technical hurdles that have constrained ssNMR’s application in antibiotic research, dramatically boosting ssNMR sensitivity and enabling selective detection of specific lipid interactions in complex membranes. This breakthrough will allow high-resolution visualization of drug-lipid interactions of antibiotics, enabling a transformative platform to elucidate the mechanism of action (MoA) of LT-antibiotics and guide the development of potent new derivatives.
To bridge a critical knowledge gap in antibiotic research, STAR will optimize the scalable bacterial production of 13C/15N-labeled phospholipids for higher yields and refine purification techniques to enhance ssNMR signal sensitivity at larger scales. Additionally, STAR will evaluate commercial feasibility and intellectual property strategies to facilitate ssNMR’s market entry. By enabling deeper molecular insights into LT-antibiotics, STAR will accelerate antibiotic research and discovery, addressing the urgent threat of AMR.
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
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug 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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HORIZON.1.1 - European Research Council (ERC)
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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-ERC-POC - HORIZON ERC Proof of Concept Grants
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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-2025-POC
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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.
3584 CS Utrecht
Netherlands
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