Objective
Malaria, can lead to the development of cerebral malaria (CM), a lethal syndrome that claims more then one million deaths per year. There is currently no effective treatment against CM. We have shown that the gas carbon monoxide (CO), generated via heme catabolism by heme oxygenase-1, inhibits the onset of CM in mice (1). While not affecting parasitemia per se, CO inhibits all the major pathologic hallmarks of CM, including blood brain barrier disruption, brain micro-vascular congestion and neuroinflammation. The mechanism underlying this protective effect relies on the ability of CO to bind the heme groups of cell free hemoglobin, released from infected red blood cells. Once bound to these heme groups CO suppresses their release, thus devoiding them from triggering CM (1). The same heme groups contained within cell free hemoglobin have been shown to scavenge endogenous nitric oxide (NO) and decrease its bioavailability, an effect shown to precipitate the onset of CM in mice (2). This suggests that as for CO, NO can also contribute to suppresses the development of CM. The central hypothesis to be tested under this proposal is that the protective effect of NO might rely on its well-established ability to induce the expression of heme oxygenase-1 and in this manner sustain the generation of CO. Once bound to the heme groups of cell-free hemoglobin, CO would inhibit heme release and in addition would increase NO bioavailability, thus generating a protective positive feed back loop in which NO would sustain the expression of heme oxygenase-1 and the generation of CO. Unveiling this functional interaction between NO and CO during Malaria infection might be useful not only to our understanding of the basic mechanisms underlying the pathogenesis of CM but also in developing new therapeutic strategies aimed at overcoming the devastating effects of this disease. 1. A. Pamplona et al., Nat Med 13, 703 (Jun, 2007). 2. I. Gramaglia et al., Nat Med 12, 1417 (Dec, 2006)
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 health sciences infectious diseases malaria
- natural sciences chemical sciences inorganic chemistry inorganic compounds
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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.
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-2007-2-1-IEF
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
1067-001 LISBOA
Portugal
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.