Objective
No single infectious agent has killed more humans historically than Mycobacterium tuberculosis (Mtb) and tuberculosis (TB) remains a leading cause of infectious mortality worldwide. Yet, only 5-10% of infected individuals develop TB. The molecular mechanisms underlying progression to active TB in otherwise healthy individuals remain poorly defined. Emerging evidence suggests that TB is not solely an infectious disease but can also be a true genetic disorder in some patients, with rare and common inborn errors of IFNγ-mediated immunity predisposing individuals to clinical disease. However, currently reported genetic causes explain only about 1% of TB cases in populations of European descent, with homozygosity for the common P1104A TYK2 variant.
This project hypothesizes that rare loss-of-function mutations in human JAK2, a central kinase in the IL-12, IL-23, and IFNγ signaling axes, predispose to TB. Through a multidisciplinary approach that combines cutting edge bioinformatic analyses, population genetics, molecular biology, and immunological profiling, this research will identify rare and common JAK2 variants in TB patients, functionally characterize their impact on JAK2-dependent signaling using overexpression systems and patient-derived cell lines and assess the consequences of these variants on anti-mycobacterial immunity in patients’ primary immune cells.
This is the first study to investigate germline JAK2 mutations as a genetic cause of infectious disease. The outcomes of this project will have high-impact translational value that can inform vaccine design, targeted therapies (such as recombinant IFNγ therapy), and genetic screening in at-risk populations, especially in light of the expanding clinical use of JAK2 inhibitors. By uncovering a hidden genetic driver of TB, this ambitious project will transform our understanding of host-pathogen interactions and support the development of precision medicine approaches to combat a resurgent global health threat.
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 infectious diseases
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine pneumology tuberculosis
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences health sciences personalized medicine
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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)
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-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-2025-PF
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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.
75015 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.