Project description DEENESFRITPL 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. Show the project objective Hide the project objective 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 medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2021-COG - ERC CONSOLIDATOR GRANTS Call for proposal ERC-2021-COG See other projects for this call Funding Scheme ERC - Support for frontier research (ERC) Coordinator UNIVERSITATSKLINIKUM BONN Net EU contribution € 1 991 250,00 Address Venusberg-campus 1 53127 Bonn Germany See on map Region Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
