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UBC Theses and Dissertations

Discovery and characterization of novel manganese-selective cation diffusion facilitators as putative anthelminthic drug targets in Caenorhabditis elegans Au, Vinci


Parasitic nematodes infect over 1.5 billion people worldwide and are a burden on the agricultural and veterinary industries. Widespread use of the few available classes of anthelmintics have led to the development of anthelmintic resistance amongst these parasitic helminths. It is imperative that we find new therapeutics to address the looming threat of anthelminthic resistance. One method for developing new chemotherapies is through rational drug design. Using C. elegans as a surrogate for parasitic nematodes, we have taken the first steps to identify and characterize a small group of putatively druggable “nematode-specific” proteins by generating null mutants and endogenously-tagged reporters using CRISPR-Cas9 gene-editing technology. To our knowledge, this work is the first to define a family of novel manganese-selective cation diffusion facilitators in C. elegans. Although these are not essential proteins and are unlikely to be good drug targets, their newly discovered role in manganese tolerance advances our knowledge of the mechanisms that underlie manganese biology and toxicity.

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