Objective
Thrombosis is a major cause of morbidity and mortality emphasizing the need for new antithrombotic therapies.
Recently, a novel pro-thrombotic mechanism was uncovered: Neutrophil Extracellular Traps (NETs). Neutrophils, the chief cells of the innate immunity, release DNA fibers during thrombosis. These extracellular DNA filaments form web-like structures known as NETs, which provide a scaffold and stimulus for thrombus formation in vitro and in vivo. Moreover, NETs are associated with thrombosis in patients underlining that NETs are a new therapeutic target.
In order to identify therapies against NETs, we propose to address the unanswered question: how are NETs neutralized in vivo? It is known that extracellular DNA is digested by cooperative action of DNase1 and DNase1-like 3 (DNase1l3) in vitro. DNase1 and DNase1l3 are the only DNases in plasma and we hypothesize that they degrade NETs within thrombi. Furthermore, we speculate that degradation of NETs causes thrombus destabilization and facilitates thrombus resolution. To test the hypothesis, we will employ DNase1- and DNase1l3-deficient mice, infusions of recombinant murine DNase1 and DNase1l3 as well as infusions of DNase1 antibodies. To address NET degradation specifically, we will use genetically engineered mice, which cannot form NETs. Using these tools, we propose to investigate the role of plasma DNases in NET-degradation in murine models of arterial and venous thrombosis.
If our hypothesis is correct, the proposed experiments will reveal the mechanism of NET-degradation in vivo and identify plasma DNases as drug candidates for antithrombotic therapy.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- engineering and technology materials engineering fibers
- social sciences sociology demography mortality
- medical and health sciences clinical medicine angiology vascular diseases
- natural sciences biological sciences genetics DNA
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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-2013-IIF
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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
20251 Hamburg
Germany
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.