As a post-doctoral researcher at Johns Hopkins University and Northwestern University under the advisement of Dr. Erik Andersen, Amanda capitalized on the genetic diversity of Caenorhabditis nematodes to identify mechanisms of resistance (MoR) to anthelmintic drugs. First, because human helminth infections are treated with drug combinations, she examined the fitness consequences when nematodes lose one or all combinations of drug targets for two drugs commonly coadministered. By measuring multiple traits (competitive fitness, fecundity, and development), she showed that resistance-associated fitness costs vary across traits. This finding has important implications for how we assess resistance. Second, she tested whether we could predict resistance-causing alleles across three nematode species. Her findings revealed species-specific patterns of drug resistance and highlighted necessary steps to accurately predict drug resistance across nematodes. Third, she exposed genetically diverse C. elegans strains to 26 anthelmintic drugs and found that individuals of the same species have vastly different responses to the same drug. This work prioritized drugs to use in genome-wide association studies (GWAS). Finally, she performed a GWAS and exposed a panel of 366 Caenorhabditis briggsae strains to seven drugs. GWAS is a powerful method for identifying genes that contribute to differences in resistance among individuals. She used an unbiased gene discovery method and identified genomic regions associated with resistance and selected candidate genes to prioritize for validation in resistance.
Amanda completed her graduate work at the University of Georgia in the laboratory of Dr. Arthur Edison in the Complex Carbohydrate Research Center. Her thesis addressed: Can we use Caenorhabditis elegans as a model to identify unknown metabolites? Untargeted metabolomics studies measure tens of thousands of features in a single biological sample. However, most features detected are unknown compounds. This creates a need for a reliable approach to identify unknown compounds. A factor contributing to the large number of unknown compounds is that metabolomics studies typically apply genetics and pathway mapping after analytical measurements are collected. The problem with this approach is that unknown spectral features are challenging to resolve outside the context of a pathway. In her graduate work, she put genetic strain selection before data collection, and thus established how hypothesized pathways can put unknown spectral features into context and help narrow possibilities during compound identification. Amanda used the model nematode C. elegans to develop, test, and validate a pipeline to identify unknown metabolites. First, she created methods to produce stable and sustainable C. elegans populations for ‘omics studies. Next, she compared three disparate study groups of C. elegans strains (i.e., genetically distinct natural strains; primary and secondary metabolism mutants) to demonstrate how an augmented design coupled with meta-analysis effectively handles known obstacles in metabolomics experiments to compare data in long-term studies. Her graduate work provided her with the expertise to use C. elegans as a model to determine how perturbations affect metabolism, a skill she is using to understand anthelmintic resistance in nematodes.
Amanda completed her undergraduate degree at the University of Kansas where she received a B.S. in Biology. As an undergraduate student, she performed research in the laboratory of Dr. Paulyn Cartwright, where she studied the evolution and development of the freshwater parasitic Cnidarian Polypodium hydriforme. Work in Dr. Cartwright's laboratory provided Amanda with her first introduction to research and helped her start her career in research.