title: A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus.
abstract: High-throughput molecular and computer technologies have become instrumental for systems biological explorations of parasites. Investigating the genomes and transcriptomes of different developmental stages of parasitic nematodes can provide insights into gene expression, regulation and function in the parasite, which is a significant step toward understanding their biology as well as host interactions and disease. This article covers aspects of a talk given at the MEEGID XII conference in Thailand in 2014. Here, we refer to recent studies of the genomes and transcriptomes of socioeconomically important parasitic nematodes of animals; provide an account of the barber's pole worm (Haemonchus contortus) and emerging drug resistance problems in this and related worms; we also propose a genomic-guided drug discovery and repurposing approach, involving the prediction of the druggable genome, prioritization of drug targets, screening of compound libraries against H. contortus and, briefly, a hit-to-lead optimization approach. We conclude by indicating prospects that molecular tool kits for nematodes provide to the scientific community for future comparative genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological and epidemiological investigations, and as a basis for biotechnological outcomes and translation.
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Preston
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Abdul
authors.initials: A
authors.lastname: Jabbar
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: robinbg@unimelb.edu.au.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Gasser
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical; D058492:Drug Repositioning / Q000379:methods; D004351:Drug Resistance; D020869:Gene Expression Profiling; D016678:Genome; D023281:Genomics / Q000379:methods; D006189:Haemonchus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D054852:Small Molecule Libraries; D059467:Transcriptome
chemical_list: D000871:Anthelmintics; D054852:Small Molecule Libraries
keywords: Bioinformatics; Drug discovery and repurposing; Drug resistance; Genomics; Parasitic nematode; Transcriptomics; Whole-organism anthelmintic screening