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Structural and functional analysis of nematode Lipid Binding Proteins (LBPs) from the chicken parasite Ascaridia galli

Objective

Bio-based agricultural production has increased in recent years and, partly in consequence, parasitic infections in free-range poultry have also increased. Ascaridiosis is one of the most widespread nematode infections of chickens and has economic impact on meat and egg production.

Intensive chemoprophylaxis is no longer efficient due to the high level of chemical residues in the food products and the rapid development of drug resistant parasites. New treatments against ascaridiosis and other nematode gastrointestinal infections are therefore necessary. Parasitic worms exhibit restricted lipid metabolism and are not able to synthesize long chain fatty acids themselves. The import of these metabolites from the host organism is critical for parasite survival and, consequently the lipid transporters are possible drug targets.

Nematodes contain two new classes of small lipid binding proteins (LBP), that are structurally different from their functional analogues in vertebrates and structural information, either global or on the active site(s), is unavailable. In Ascaridia galli two LBP are found: Ag-NPA-1 and novel 55 kDa protein, Ag-lbp55. The objective of the proposal is to obtain detailed structural and functional information about these proteins and their importance for parasite survival.

This will be done by studying the binding affinities of specific ligands for Ag-lbp55. Structural information on Ag-NPA-1 and Ag-lbp55 in the presence or absence of ligand will be obtained, either using crystallography, small-angle X-ray scattering, or NMR, thus identifying the active sites and generating an understanding of the relationship between the two lipid binding proteins.

The information obtained will be further verified for different helminths as well as the free-living nematode C. elegans. The outcome will be information on the lipid transport mechanism in nematodes and its role in parasite-host interactions.

Call for proposal

FP6-2004-MOBILITY-5
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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Address
Meyerhofstrasse 1
Heidelberg
Germany