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Research pioneered the simple model organism Drosophila in order to provide insight into human neurodegenerative disease, generating a model in the fly for one of the human trinucleotide repeat diseases. Model revealed conservation of specific aspects of disease found in humans, thus initiating a vigorous research area of using invertebrate models to reveal mechanisms of various human diseases. Continued to work along these lines, establishing new models for disease and identifying genes that contribute to, or mitigate, aggregates typically associated with neurodegeneration. These studies have included the discovery of molecular chaperones as modulators of disease protein toxicity, and of a role of RNA biology in disease processes. With collaborators, used insight from fly gene interactions to reveal new human mutations that contribute to motor neuron disease. Introduced, for example, a new application for model organism genetics that has relevance for understanding neurodegenerative disorders.