Project description
Targeting toxin-related amyloids of Staphylococcus aureus
Usually found on human skin and in the nose, the bacteria Staphylococcus aureus can eventually become pathogenic, causing community and healthcare-acquired infections. Using atomic force microscopy alongside complementary multiscale biophysical tools, the EU-funded PSMNano project aims to study the role of toxins, called phenol-soluble modulins (PSM), secreted by S. aureus and highly associated to their virulence. Researchers are notably interested in investigating how PSMs interact with host membranes and cause either cytotoxicity or inflammation, depending on the structure they adopt (monomeric vs. fibrils). Understanding the fundamental roles of PSM in S. aureus pathogenesis is fundamental to the identification of therapeutic targets and the design of novel treatments, eliciting less resistance than traditional antibiotics.
Objective
Phenol-soluble modulins α3 (PSMα3) are functional amyloids involved in the virulence of Staphylococcus aureus, a multi-drug resistant pathogen under the surveillance of the European Union (EU). The project PSMNano aims at unveiling the molecular mechanisms driving PSMα3 interactions with cell membranes, which lead to their cytotoxic and proinflammatory activities, with a focus on the impact of amyloid fibrillation. So far poorly known, dissecting those mechanisms is yet critical to efficiently target PSMα3 activities, in turn S. aureus pathogenicity, and avoid the pandemics foreseen by the EU in the coming decades. Thanks to atomic force microscopy coupled to complementary multiscale biophysical tools, PSMNano will provide high spatiotemporal resolution multiparametric imaging of those interactions, while quantifying their affinity and energetic landscape, on both mimetic models and living cells. Remarkably, single-molecule experiments and cell budding will help decipher the forces driving the FPR2 receptor-dependent role of PSMα3. The expertise of the fellow Dr. Mathelié-Guinlet in surface chemistry and nanobiophysics related to bacterial virulence, the complementary knowledge she will acquire from the supervisor Pr. Molinari on membrane models design and spectroscopic investigations of amyloids, and the cutting-edge technical platforms of the host institution, CBMN (University of Bordeaux, France) will be instrumental for the success of this interdisciplinary project. The fundamental insights brought by the understanding of the role of PSMs-cell membrane interactions in S. aureus pathogenesis could set the stage for the design of novel therapeutics, e.g. inhibitors of PSMα3 activity. PSMNano could also open up avenues for standardized protocols to characterize amyloid-membrane interactions, involved in degenerative diseases. With valuable short- and long-term outcomes, this project will undoubtedly strengthen the competitiveness of the EU health program.
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.
- medical and health sciences health sciences public health epidemiology pandemics
- natural sciences physical sciences optics microscopy
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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)
MAIN PROGRAMME
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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
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) HORIZON-MSCA-2021-PF-01
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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.
75794 Paris
France
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.