Objective
Group A streptococcus (GAS) is a major, human specific, bacterial pathogen. Most people suffer from mild infections, while only a few develop invasive GAS (iGAS) infections. These cases of iGAS infections are unexplained as they strike otherwise healthy people. The human specificity of GAS and the interindividual variability upon infection with GAS are poorly understood. My proposal aims to close both knowledge gaps: I hypothesize that single-gene defects of antistreptococcal immunity increase susceptibility to human-specific GAS virulence factors in some people, thereby underlying their iGAS infections.
I propose an innovative framework to unravel iGAS pathophysiology in humans, by applying a strategy to integrate the studies of human genetics and host-pathogen interactions at the molecular level. This project focuses on patients suffering from iGAS infections. Most patients have been enrolled, sampled, and whole exome sequencing (WES) performed. Additional patients will be recruited. The human gene(s) underlying iGAS infections will be identified using complementary WES-based approaches. The discovered inborn error(s) of immunity to GAS and the host-pathogen interactions will be dissected at the molecular, cellular, tissue, and whole-organismal levels, including with patients’ cells and clinical GAS strains.
The immediate availability of patients’ genetic data provides a secure starting point for an efficient implementation of this proposal. Preliminary analyses have yielded two promising candidate genes. Access to patients’ specimens and clinical GAS isolates offers an exceptional opportunity to characterize patient-specific host-pathogen interactions. Thus, we are in a unique position to discover the first human genetic determinant(s) of iGAS host-pathogen interactions. This project may uncover the role of genes in human physiology beyond the infectious phenotype and accelerate the development of preventative strategies against GAS infections.
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.
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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.
3584 CX Utrecht
Netherlands
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.