Objective
Filarial nematodes of man, like most helminth parasites, are long-lived organisms which persist in the mammalian host despite a vigorous and sustained immune response. The ability to neutralize or subvert host immunity is thus crucial to their survival. Characterization of parasite molecules involved in this process and dissection of the associated mechanisms will not only provide a focal point for the development of chemotherapy and immunoprophylaxis against filariasis, but will also provide basic information on immune effector mechanisms against complex multicellular parasites. We intend to focus upon anti-oxidant enzymes, which we propose are a primary line of defence against host immunity and the project will include studies on the three major filarial nematode parasites of man: onchocerca volvulus, Wuchereria bancrofti and Brugia malayi.
We will complete the characterization of the genes for glutathione peroxidase (GSHPX) and superoxide dismutase (SOD) from 0. volvulus and Brugia, determine whether these encode distinct cytosolic and secreted enzymes and define (where possible) their expression in different stages. We will then develop antibody reagents to expressed gene products and utilize these to determine the localization of the native enzymes in different stages via immuno-electronmicroscopy. Enzyme secretion will be monitored in vivo with these reagents, and measured both biochemically and immunologically in vitro. The immune response to anti-oxidants will be assessed in Indian patients infected with W. bancrofti, most specifically by measuring antibodies which inhibit and/or bind parasite enzymes. The putative protective role of these enzymes against damage and killing by reactive oxygen metabolites will be assessed in vitro, primarily with different stages of B. malayi, by measuring the extent and site of lipid peroxidation in relation to the activity of parasite anti-oxidants. Particular attention will be focused upon the cuticle, and freeze fracture analysis will be employed to assess immune-mediated damage to cuticular membrane structures. The effect of enzyme inhibitors and inhibitory antibodies will also be determined, which will define the suitability of these molecules as targets oE chemo- or immuno-prophylaxis.
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 immunology
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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.
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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
20359 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.