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Large-scale ecological sampling can be difficult and costly, especially for organisms that are too small to be easily identified in a natural environment by eye. Typically, these microscopic floral and fauna are sampled by collecting substrates from nature and then separating organisms from substrates in the laboratory. In many cases, diverse organisms can be identified to the species-level using molecular barcodes. To facilitate large-scale ecological sampling of microscopic organisms, we used a geographic data-collection platform for mobile devices called Fulcrum that streamlines the organization of geospatial sampling data, substrate photographs, and environmental data at natural sampling sites. These sampling data are then linked to organism isolation data from the laboratory. Here, we describe the easyFulcrum R package, which can be used to clean, process, and visualize ecological field sampling and isolation data exported from the Fulcrum mobile application. We developed this package for wild nematode sampling, but it can be used with other organisms. The advantages of using Fulcrum combined with easyFulcrum are (1) the elimination of transcription errors by replacing manual data entry and/or spreadsheets with a mobile application, (2) the ability to clean, process, and visualize sampling data using a standardized set of functions in the R software environment, and (3) the ability to join disparate data to each other, including environmental data from the field and the molecularly defined identities of individual specimens isolated from samples. [ABSTRACT FROM AUTHOR]

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control. [ABSTRACT FROM AUTHOR]

Many chemotherapeutic drugs are differentially effective from one patient to the next. Understanding the causes of this variability is a critical step towards the development of personalized treatments and improvements to existing medications. Here, we investigate sensitivity to a group of anti-neoplastic drugs that target topoisomerase II using the model organism Caenorhabditis elegans. We show that wild strains of C. elegans vary in their sensitivity to these drugs, and we use an unbiased genetic approach to demonstrate that this natural variation is explained by a methionine-to-glutamine substitution in topoisomerase II (TOP-2). The presence of a non-polar methionine at this residue increases hydrophobic interactions between TOP-2 and its poison etoposide, as compared to a polar glutamine. We hypothesize that this stabilizing interaction results in increased genomic instability in strains that contain a methionine residue. The residue affected by this substitution is conserved from yeast to humans and is one of the few differences between the two human topoisomerase II isoforms (methionine in hTOPIIα and glutamine in hTOPIIβ). We go on to show that this amino acid difference between the two human topoisomerase isoforms influences cytotoxicity of topoisomerase II poisons in human cell lines. These results explain why hTOPIIα and hTOPIIβ are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses. [ABSTRACT FROM AUTHOR]