Objective
Neutrophils are short-lived leukocytes with vital functions in host defense. Neutrophils are massively recruited to extravascular sites in response to danger signals. This immediate, life saving, inflammatory response can turn against the host if its intensity and duration are dysregulated leading to tissue injury and/or failed immune response to pathogens. The dual protective/pathologic role of neutrophils is reflected by the functions of neutrophil serine proteases, potent granule enzymes that hydrolyze other proteins. Neutrophil serine proteases (or NSPs) directly kill pathogens after fusion of the NSP-rich granules with the microbe-containing phagosome. However, when released extracellularly and in excess of the anti-protease shield, NSPs are harmful by fueling the inflammatory response and by destroying extracellular matrix proteins and immune defense proteins. The aim of the proposed work is to investigate the regulation of NSPs by the serpin (SERine Protease INhibitors) family of proteins in health and disease. Specifically, we will study the role of serpinB1, one of the best inhibitors of the three NSPs: neutrophil elastase, cathepsin G and proteinase-3. We have previously shown that (i) serpinB1, a cytoplasmic inhibitor of NSPs carried at high levels in neutrophils, provides a physiological and vital shield against pathologic actions of NSPs during lung infection, and (ii) serpinB1 prevents the early death of neutrophils during infection. Our preliminary data now indicates that serpinB1 is required to preserve the size of the neutrophil reservoir in bone marrow and protects lung epithelial cells against NSPs. The proposed work will elucidate the protective functions of serpinB1 in myeloid cells and lung epithelial cells. Overall, these studies will provide highly significant advances in understanding pathologic mechanisms due to excess NSPs in bone marrow homeostasis and pulmonary disease.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine physiology homeostasis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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.
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.
FP7-PEOPLE-2009-RG
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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.
Coordinator
3012 Bern
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.