Project description
Understanding Lpt functional mechanism to combat antimicrobial resistance
Antimicrobial resistance is a global health threat. Resistant Gram-negative bacteria, which have a protective membrane barrier, make antibiotics ineffective. Targeting the lipopolysaccharide (Lpt) protein complex that supports this barrier may combat resistance. With the support of the Marie Skłodowska-Curie Actions programme, the LpTarget project will explore the functional mechanism of Lpt, focusing on the insertion of lipopolysaccharides into transport machinery. By integrating advanced computational techniques with structural biology in a native membrane environment, the project will enhance our understanding of Lpt structure and function. This could lead to new strategies for disrupting gram-negative bacterial barriers and advancing Lpt-based drug discovery.
Objective
Antimicrobial resistance is a global public health threat and a top priority concern in Europe with estimated 1,27 million annual deaths worldwide and 35,000 in Europe. Many of these deadly infections are caused by resistant Gram-negative bacteria which are undermining our therapeutic options because antibiotics are no longer effective. These bacteria are coated by two membranes where the one exposed to the environment is made of lipopolysaccharide—a toxic glycolipid which forms a barrier hampering the penetration of compounds, including antibiotics. These bacteria possess the Lpt multiple protein complex that bridges the two membranes and transports this essential glycolipid from the inner to the outer membrane. Target the Lpt to weaken the Gram-negative barrier, enhances antimicrobial permeability and is a viable approach to fight resistance.
In this project, we will employ an interdisciplinary biophysical and computational approach to advance the currently limited knowledge of the Lpt functional mechanism, necessary for effective targeting. We will uncover how lipopolysaccharide is inserted into the machinery and squeezed out from protein to protein along the bridge. The project will integrate cutting-edge computational techniques with structural biology in a native membrane environment to bridge the knowledge gap of Lpt structure and function at the molecular level. Molecular dynamics simulations will complement Lpt cryo-EM structures by exploring the complex dynamics and regulations of the transport machinery. The project will create new research avenues to weaken the Gram-negative bacterial barrier and advance progress in Lpt-based drug discovery. Its findings will establish a knowledge framework transferable across ESKAPEs, serving as an agile resource to prevent future global outbreaks of 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 biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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)
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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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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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38058 Grenoble
France
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