Project description
The role of mammalian guard sensors in immunity against pathogens
Pathogens use virulence factors to inhibit immune defences, but host guard proteins monitor these pathways and activate guard-driven immunity when needed. The MORC3-MRE pathway is the first mammalian guard-sensing pathway known to trigger a protective response to viral activity. The ERC-funded GUARDIANS project will explore the role of mammalian guard sensors in immune homeostasis and defence, with a focus on the MORC3-MRE pathway. Using genetic approaches in human monocytes and mice, the project aims to uncover new components and molecular mechanisms of this pathway and examine its role in immunity. Additionally, it will identify pathogen virulence activities detected by the immune system and test the concept of guard immunity in mammalian defences.
Objective
Successful pathogens use virulence factors to inhibit immune defenses. To counteract this, host guard proteins monitor the integrity of pathways (guardees) that are attacked by virulence factors, such that inhibition of the guardee activates guard-driven immunity. Instead of directly detecting microbial components like canonical innate immune (pattern recognition) receptors, guards are activated by sensing the activity of virulent microbes. While guard-immunity is common in plants, only a few mammalian guard-pathways are known and mammals are thought to heavily rely on pattern recognition to detect pathogens. We have recently described the MORC3-MRE pathway, the first mammalian guard-sensing pathway that recognizes the virulence- associated activity of viruses to induce a protective interferon (IFN) response. I hypothesize that mammalian guard-sensors are highly relevant for both immune homeostasis and immunity and propose to test this hypothesis by focusing on the MORC3-MRE pathway. Utilizing genetic approaches in human monocytes and mice, we will reveal novel components and molecular mechanisms of the MORC3-MRE pathway and investigate its role in homeostasis and immunity in vivo. The main hypothesis of this proposal is that guard- sensing allows mammalian immune cells to broadly recognize the activities of virulence factors. We aim to conduct forward genetic screens in human monocytes to identify virulence-associated activities of pathogens that are sensed by the immune system. Functional genomics and biochemical approaches will identify the attacked guardee, the guard-sensor and molecular mechanism of guard-sensing. In summary, we will experimentally test the novel concept of guard-immunity in mammalian immune defenses. These experiments will generate fundamentally new insights into molecular mechanisms of pathogen recognition and will significantly broaden our understanding of innate immunity and host-pathogen interactions.
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
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences zoology mammalogy
- medical and health sciences basic medicine physiology homeostasis
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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)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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1030 Wien
Austria
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