Project description
Investigation of the fundamental principles of sterile inflammation
Inflammation represents a natural mechanism to restore tissue homeostasis, while its deregulation causes disease. The ERC-funded FIREALARM project will focus on the fundamental mechanisms of the physiological origin of inflammation using organismal-, cellular- and molecular-level approaches. The project will examine the central hypothesis that endogenous intercellular signalling proteins drive sterile inflammation and shift homeostatic stable to non-resolving chronic states. Newly developed secretomics, including cell type specific mass spectrometry, will identify inflammatory signals in vitro and in vivo. The goal is to achieve a better understanding of the molecular and organismal signalling circuits governing homeostasis and develop strategies to treat chronic conditions.
Objective
Inflammation is a natural mechanism to restore tissue homeostasis, and its deregulation causes human disease. The programmed cell death form pyroptosis elicits inflammation in a cell-autonomous and non-autonomous fashion by releasing cytokines and ‘danger’ signals. Intriguingly, immune pathology independent of cytokines has alluded to unexplored signaling circuits between cells regulating pyroptotic inflammatory reactions.
FIREALARM addresses the fundamental question of the physiological origin of inflammation using convergent system-wide, organismal, cell biological, and molecular approaches. We will test the central hypothesis that endogenous intercellular signaling proteins drive sterile inflammation and shift homeostatic stable to non-resolving chronic states. We will determine paracrine activities of pyroptosis by systematic, iterative ablation of molecule release from dying and perception pathways of sentinel cells. In a complementary approach, we will identify inflammatory signals in vitro and in vivo by newly developed cell type-specific mass spectrometry-based secretomics technologies. Holistic views of intercellular signaling proteins, their exposure, and modification will determine the molecular language orchestrating communication networks between cells and enable the recognition of signals initiating, amplifying, and resolving inflammation. We will achieve a new level of molecular and organismal understanding of intercellular circuits governing homeostasis and conceive strategies to revert chronic conditions. Emerging inflammatory cell death markers will stratify molecular etiology and outcome of patients with sterile inflammatory diseases.
Together, FIREALARM tackles the fundamental principles of sterile inflammation relevant for understanding the pathogenesis of chronic metabolic and age-related disorders.
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 cell biology cell signaling
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
- 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.1.1 - 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
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-2021-COG
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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.
53127 Bonn
Germany
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