Prof. Adrian Wolstenholme - C. elegans as a model for ascarid parasites; levamisole receptors

Réalisation : 30 novembre 2021 Mise en ligne : 30 novembre 2021
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Ligand-gated ion channels provide an excellent test for any expression system and for C. elegans as a model for parasitic nematode species, including the ascarids. They are complex proteins made of multiple subunits which are encoded by a large gene family, that carry multiple post-translational modifications and which exhibit varied physiological and pharmacological properties. This last property makes them excellent drug targets and provides a fairly simple way of testing the accuracy of any comparison between native and recombinant channels. The levamisole receptor is an excellent illustration; in C. elegans full expression of a levamisole-sensitive receptor in Xenopus oocytes is reported to require 8 proteins, 5 subunits and 3 chaperones. Some years ago we were able to generate levamisole-sensitive receptors by expressing just two subunits. We have also tried to rescue C. elegans mutant strains by over-expression of parasite subunits; whereas UNC-38 and UNC-29 from the clade V parasite H. contortus were able to rescue the mutations, those from Ascaris were less effective. Overall, my feeling is that although C. elegans is a convenient experimental system in many ways, its usefulness for ascaris research will vary on a gene by gene basis, which makes routine prediction and extrapolation unreliable.


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