Objective
An important challenge in biophysics is to understand the complex biological functions emerging from the physico-chemical properties of simple building blocks. Showcasing this challenging question is the multiple functions achieved by the phenol soluble modulins (PSMs) peptides from Staphylococcus aureus, able to self-assemble into amyloid structures, and underlying S. aureus pathogenicity. Over the past decade, the intrinsic capacity to form fibrils in vitro has been directly correlated with the peptide biological activities in vivo. This traditional focus severely limits our understanding of the role of more complex intermediate structures and dynamic interactions with the encountered biological membranes. Here, I propose to uncover the molecular determinants and mechanisms of self-assembly and its implication in dictating PSMs multifunctionality, from biofilm formation to inflammation and toxicity. I hypothesize that, beyond the current one structure one function paradigm, intermediate assemblies are the membrane active entities and their co-aggregation with membrane components, such as lipids and proteins, contribute to their distinct functions. Building on my prior work on PSM3 and my leading force in single-cell and single-molecule characterizations, I will:
1. Reveal the mechanism of self-assembly and the role of lipid co-factors
2. Uncover the molecular modes of action of diverse assemblies at the membrane interface
3. Establish in vivo how these assemblies drive host cell inflammation and death
4. Explore the role of self-assembly in bacterial adhesion, in turn biofilm formation
By pinpointing the key characteristics of PSMs assemblies, from their physico-chemical to structural properties, responsible for their different functions, this project could set the basis for the design of novel structure-based therapeutics against staphylococcal infections, eliciting less antibio-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 biochemistry biomolecules proteins
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biophysics
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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.
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 - HORIZON ERC 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-2024-STG
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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.