The nematode cuticle is a collagenous extracellular matrix that is synthesised repeatedly during development via the moulting process. The enzymology of cuticle collagen biosynthesis and more importantly the enzymology of cuticle ecdysis and moulting represent potential novel targets for parasitic nematode control. Using C. elegans we have identified and characterized key moulting enzymes and have focused on the nematode astacin (NAS) metalloproteases. As an example, mutation of the enzyme-encoding genes NAS-36 and NAS-37 reveals an essential developmental role for these enzymes in C. elegans moulting. We have identified the orthologs in the diverse parasitic nematodes Brugia malayi and Haemonchus contortus that are able to rescue the moulting phenotypes associated with
nas-36/ -37.Using in silico-modelling we have screened available chemical libraries and have tested several hundred potential inhibitors using in vivo and in vitro assays in C. elegans, Brugia malayi and Haemonchus contortus.The screening process will be described and the main finding of this study will be presented.