Conference Agenda
Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).
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CP12: Sheep & Goats - 10 min talks Location: Lecture Theatre 2 Session Chair: Vern Bowles, The University of Melbourne Session Chair: Nichola Calvani, The University of Sydney | |
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Chemical perturbation reveals a cytoskeletal–trafficking vulnerability in Haemonchus contortus 1: Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, Victoria 3010, Australia; 2: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; 3: Melbourne Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia; 4: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland Phenotypic screening readily identifies compounds that impair worm motility or development, the intrinsic biological processes underlying chemical sensitivity in parasitic nematodes remain poorly defined. Here, we identified a hit compound with a pyridyl scaffold from a phenotypic screen against the parasitic nematode, Haemonchus contortus, and using structure–activity optimisation we generated a potent chemical probe, WEHI-864. To uncover protein networks associated with the mechanism of action, thermal proteome profiling and time-resolved quantitative proteomics interrogated WEHI-864-induced perturbations in H. contortus. Across larval and adult stages of this major parasite of livestock, proteome integral solubility alteration (PISA) assay revealed reproducible alterations in proteins associated with cytoskeletal organisation and intracellular trafficking, including actin- and motor-related components. Complementary quantitative proteomics identified induction of an aspartyl protease and suppression of secretory CAP family proteins. Integrated analysis of these datasets supports a model in which chemical perturbation of cytoskeletal and trafficking proteins is associated with secondary modulation of proteolytic pathways, coinciding with rapid impairment of motility. These findings indicate that linked structural and proteolytic responses contribute to chemical sensitivity in H. contortus and demonstrate how integrative proteomics can resolve organism-level responses to chemical perturbation beyond single-target paradigms. | |