Methods of Maintaining and Utilizing the Caenorhabditis elegans Model for Investigations of Agrochemical Toxins in Huntington’s Disease

Science Center, Bent Corridor

Expression of mutant huntingtin protein (Htt) in humans causes Huntington’s disease (HD), which is a genetic autosomal dominant neurodegenerative disorder. HD is characterized by selective loss of medium spiny neurons (MSNs) in the striatum. The striatum is located in the subcortical area of the forebrain, and it plays a large role in the initiation of movement as a major component of the basal ganglia circuitry. The striatum is also the brain region most vulnerable in HD. Emerging scientific evidence suggests that environmental toxins play important roles in modulating the onset of HD and its progression Previously, I investigated the effects of a commonly used pesticide chlorpyrifos (CPF) in a cell, or in vitro, model of HD. My aim in the current project is to translate my previous work in vitro to an in vivo model. The importance of doing research in vivo—in the biological system of a living creature—vs. in vitro—outside of the biological context—is that observations can be more closely related to human beings. Caenorhabditis elegans (C. elegans) is a non-parasitic round worm used frequently as an in vivo, or living, model for biomedical research. This species of nematode is one of the few animal models with a sequenced genome, thus allowing researchers to identify genes and their respective expressions in healthy and disease conditions. The various genes have mammalian homologues and can be observed and/or manipulated according to the experimenter’s scientific aim. This allows for more accurately designed treatments for humans. My research goal is to learn and master some of the most common methods used in maintaining and utilizing the C. elegans animal model. Some of the common techniques for C. elegans maintenance and experimental utilization include synchronization, treatments, lethality assays, RNA extraction, microscopy, chunking and worm picking. Recognizing the homologous genotypes between mammals and C. elegans, we hypothesize that CPF exposure in an HD strain of C. elegans would have similar effects to those observed in the MSNs of mouse striatal models.