Objective
"Every year over 400.000 EU citizens suffer from sepsis and every third of them dies due to the severity of this systemic inflammation. The mortality results from excessive neutrophil activation leading to vasculature malfunctioning and subsequent multiorgan failure.
Recently, we (outgoing host) revealed that during bacterial sepsis neutrophils activated by platelets release NETs (neutrophil extracellular traps) that trap and kill bacteria but this occurs at the expense of injury to endothelium (Nature Medicine, 2007, 13: 463-9).
NETs are web-like structures composed of DNA and proteins released from neutrophil granules, including proteases such as MMP-9 (matrix metalloproteinase 9) and NE (neutrophil elastase). We (researcher) showed that the proteases co-facilitate migration of neutrophils (J Leukocyt Biol, 2009, 85: 374-81) and we (return host) pointed out MMP-9 inhibitors as therapy for acute inflammatory diseases (Nature Rev Drug Discovery, 2007, 6: 480-98).
We propose a novel concept that the damage to blood vessels occurring during sepsis is a consequence of NET formation and results from protease activity. This is strengthened by observation that damage to endothelia is detected in sepsis and when NET formation is blocked no injury is noticed.
Therefore we will address the hypothesis that proteases (MMP-9, NE) attached to NETs cause injury to endothelial cells through the following specific aims:
-evaluation of endothelial damage in transgenic mice deficient in either MMP-9 or NE
-determination of intercellular and inter-protease events leading to the injury
-identification of endothelial substrates of MMP-9 and NE.
The experiments will implement state of the art methodologies including intravital microscopy and multidimensional degradomics.
Overall, the studies will elucidate NET-linked protease-dependent mechanisms leading to the damage of endothelium and will point out targets for new therapies in sepsis."
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- social sciences sociology demography mortality
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences health sciences inflammatory diseases
- natural sciences physical sciences optics microscopy
You need to log in or register to use this function
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-2010-IOF
See other projects for this call
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
3000 Leuven
Belgium
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.