Objective
Interaction between the immune and nervous systems is critical for repair, tumour surveillance and protection from infection. Toll-like receptors are evolutionarily ancient pattern-recognition receptors that are implicated in innate responses to infection. In work done in Canada we have shown that signals delivered through the Toll-like receptor-2 (TLR2) are critical for early microglial response to experimental brain injury. Microglia are macrophage-like cells in the brain and spinal cord that act as rapid sensors of loss of homeostasis of any kind. Activated microglia can recruit T cells and macrophages to the central nervous system via production of chemokines and cytokines.
Our findings suggest that endogenous ligands for TLR2 are produced within the brain independent of infection and these ligands direct microglial response. This represents a novel role for TLR's in brain function. In Denmark, we propose to identify TLR2 ligands that are produced in response to injury in the mouse brain. Localized axona l degenerative injury will be used to induce TLR2 ligands. These will be assayed for their ability to induce intercellular signals, and mRNA and protein for specific cytokines and chemokines in microglial cultures.
Criteria for functional TLR2 ligands will include purification with TLR2-Fc but not TLR4-Fc fusion proteins, and induction of responses in wild-type but not TLR2- or signalling-deficient microglia, that are blocked with TLR2- specific reagents. Ligands that meet these criteria will be characterized by proteomic analysis including 1- and 2-D gel electrophoresis, immunoblotting and mass spectrometry. Ligands are expected to be lipoproteins or peptidoglycans - our assays will detect both. Ligand-specific monoclonal antibodies will be generated and used to probe location and function. Long-term goals include gene manipulation in animal models.
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 neurobiology
- natural sciences biological sciences cell biology cell signaling
- natural sciences chemical sciences electrochemistry electrophoresis
- natural sciences chemical sciences analytical chemistry mass spectrometry
- medical and health sciences basic medicine physiology homeostasis
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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.
FP6-2004-MOBILITY-12
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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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
ODENSE M
Denmark
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.