Summary
The goal of the project was to conduct fundamental research with a focus on finding new solutions to internal parasitic diseases of sheep using genomic, bioinformatic and chemical approaches. The characteristics of genes associated with reproduction and/or development were defined. The achievements provide a foundation for the development of new compounds with activity against selected nematodes. The predominant focus was on the barber's pole worm, Haemonchus contortus.
The key achievements of the project were:Construction of molecular archives for Haemonchus contortus;Microarray expression profiling of this nematode;Bioinformatic analysis of ESTs and prediction of functions based on comparison ofmolecules in current databases;Identification and characterization of a subset of seven molecules involved in keybiological pathways and considered (based on phyloGenetics and genomics) to be 'specific'to nematodes;Isolation of full-length cDNAs and/or genes and cloned for subsequent expressionConsolidation of a technology pipeline for drug target and drug discovery;Testing of a range of chemical compounds and identification of a subset withnematocidal effects.
Using the integrated technology platform developed, a multi-phase, genomic-bioinformatic pipeline was employed to identify candidate drug targets, taking advantage of nematode and mammalian sequence information available in current gene databases, and incorporating gene function data from the free-living nematode C. elegans to deduce a set of 'nematode-specific' molecules, whose interruption or disruption is known to adversely affect nematode development, reproduction and/or survival. The focus was on the trichostrongylid nematode H. contortus, which is of economic importance in Australia and worldwide. Any outcomes for this nematode also have major implications for other related nematodes of livestock.
