Objective
The cGAS-STING pathway is a central component of the innate immunity that detects cytosolic double-stranded DNA (dsDNA). Upon sensing dsDNA, cGAS produces cGAMP, a second messenger that binds to and activates STING, thereby inducing various antiviral gene expression and promoting the production of proinflammatory cytokines and chemokines. While transient activation of this pathway is essential for host defense, persistent activation is deleterious and has been linked to autoimmune and autoinflammatory diseases. To prevent such chronic responses, cells employ regulatory mechanisms to timely terminate the cGAS-STING signaling, such as by trafficking activated STING to lysosomes for degradation.
However, how cGAMP itself is regulated following STING activation remains poorly understood. Preliminary data from the host laboratory and others indicate that intracellular cGAMP levels are transient, suggesting the existence of additional, yet unidentified, regulatory mechanisms. The applicant hypothesizes that cells may employ active secretion, enzymatic degradation, or sequestration processes to eliminate residual cGAMP and thereby prevent sustained activation of innate immunity.
To address this, the project will synthesize a series of fluorescent cGAMP analogs as proxies to identify regulatory mechanisms of cGAMP via live-cell super-resolution microscopy and FACS. Furthermore, systematic and unbiased CRISPR screens will be employed to discover genes involved in the cell-autonomous control of cGAMP, followed by biochemical and structural studies to elucidate the molecular mechanisms of cGAMP regulatory proteins.
By uncovering how cells clear cGAMP after STING activation, this project will illuminate a critical yet unexplored aspect of innate immune regulation. Identifying the molecular regulators of cGAMP homeostasis may reveal new pathways contributing to autoimmunity and autoinflammation, providing novel opportunities for therapeutic intervention.
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 genetics DNA
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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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.
1015 Lausanne
Switzerland
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.