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Adaptation of Caenorhabditis elegans technology to express and identify parasite target genes


There are about 82 million cattle in the EU, most of which are exposed to infection with gastro-intestinal nematodes at grazing, with resultant, often substantial, impaired production efficiency. The most common and most pathogenic of these nematodes is Ostertagia ostertagi, which infects the abomasum of cattle.

Control of O. ostertagi in Europe is based almost exclusively on the use of anthelmintic drugs. However, these drugs have several drawbacks such as the high costs, interference with natural immunity, drug residues in food products and in the environment and the increasing incidence of parasite resistance against the anthelmintics. Vaccination is being considered as the most feasible alternative to anthelmintics.

Recently, we identified three excretory-secretory antigens from O. ostertagi which induced practically useful levels of protection (~60% in faecal egg counts) in calves against a homologous infection. Unfortunately, it is practically unfeasible to harvest large quantities of the native antigens for vaccine production on a large scale.

The challenge now is to produce these antigens in an immunologically active form using DNA technology. Recombinant versions of several gastrointestinal nematodes antigens, produced in bacteria, yeast or insect cells, have proven to be largely ineffective.

Glycan is strongly implicated in protection, is quite unique to nematodes and is predicted to be highly immunogenic. A solution is to develop an expression system in the free-living nematode C. elegans where post-translational modifications closely resemble those found in parasitic nematodes.

Focussed work is required to improve the level of expression by investigating the use of different promoters and different sites of expression in C. elegans tissues. This is the primary focus of the present proposal.

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Pentlands Science Park, Bush Loan
United Kingdom