Objective
According to the European Cardiovascular Disease Statistics 2012 edition, over a third of deaths from cardiovascular disease in the EU are from coronary heart disease and just over a quarter are from stroke. But there is a lack of effective treatment for most stroke patients. Despite an expanding understanding of the cellular and molecular mechanisms underlying ischemia/reperfusion injury, 1000+ experimental compounds have failed at some stage of development. Thus, innovative therapeutic approaches are needed to develop an effective treatment for stroke. Preconditioning (in which a stimulus below the threshold of damage is applied, leading to tissue resistance to the same, or different stimuli given beyond damage threshold) is an attractive experimental strategy to identify endogenous protective mechanisms that could be therapeutically implemented. The proposed studies will identify a key molecular interaction underlying endogenous protective mechanisms induced by preconditioning and its potential to be exploited therapeutically.
The lipid mediator sphingosine 1-phosphate (S1P) plays a role in preconditioning, protecting the heart and kidney against ischemia/reperfusion injury. Sphingosine kinase 2 (SK2) is the major S1P-synthezising enzyme in brain and is up-regulated in neurons in response to ischemia. SK2 is a BH3-only protein, that can interact with the cell death-related protein Bcl-xL, suggesting that this enzyme isoform has S1P-independent actions. Two specific aims will test in vivo and in vitro the hypothesis that various preconditioning stimuli induce tolerance to brain ischemia by a novel common mechanism involving both S1P-mediated autocrine/paracrine mechanisms (HIF1alpha - SK2 - S1P receptors - Akt - nitric oxide synthase) and intracellular protein-protein interactions inducing protective autophagy.
This project will identify novel therapeutic targets and will provide a route for translation to clinical research.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences clinical medicine cardiology cardiovascular diseases
- medical and health sciences basic medicine neurology stroke
- 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-2013-CIG
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
T12 YN60 Cork
Ireland
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.