Nearly one billion people worldwide have a neurological disease, and one out of every six adults in the United States has a mental illness. For rare and severe neurodevelopmental disorders, like Timothy syndrome (TS), exact genetic causes have been identified and studied extensively. TS is caused by a single point mutation in CACNA1C, a voltage-gated calcium channel (VGCC), which results in severe developmental defects, cardiac arrhythmia, and autism. Studies using patient derived cells are useful in identifying impaired cellular function, especially for TS and other neural activity-dependent disorders. Also, functional high-throughput screening assays that use disease-relevant cell types can lead to more targeted therapeutics that regulate cellular activity. Although these approaches are promising, cell-based assays do not consider the diversity of disease pathology or efficacy of broad-acting therapeutics in multi-cellular organisms. Therefore, we developed several whole-organism disease models using CRISPR-Cas9 and transgenes in the nematode C. elegans that harbor human VGCC mutations. We evaluated and identified behavioral, morphological, and functional phenotypes, and invented new high-throughput functional screening technologies to identify transient and potent suppressors of neural activity in these animals. We expect that these new disease models and methods will provide a pipeline for investigating activity- dependent neurological disorders in whole organisms to identify more effective therapeutics. Altogether, we aim to deepen our understanding about the brain and discover treatments for the millions of individuals that suffer from neurological disease.

A new rapid computer assisted micro-titer plate interferon assay system was developed and characterized for use in high capacity clinical and research applications. The biological aspect of the assay was a modification of the assay methods of Finter, Armstrong and McManus. It was an application of spectrophotometric quantification of the reduction of viral cytopathic effect (CPE) as reflected by neutral red dye uptake by viable cells. A computer program was developed for the extrapolation of raw data to reference interferon units.