Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Fetal Alcohol Spectrum Disorder (FASD) costs Canada $4 billion a year. FASD includes a variety of physical and neurobehavioral complications caused by prenatal alcohol exposure. The types and severity of symptoms depends on 3 major factors (exposure pattern, genetic and/or environmental backgrounds). However, some research showed that symptoms can vary even between monozygotic twins raised together. This phenotypic variation unrelated to genetic and environmental factors has been described as "intangible variation", which is often observed in complex disorders such as schizophrenia. I hypothesized that intangible variation may be caused by different gene expression pattern between individuals, and the restoration of expression pattern to normal levels can attenuate specific symptoms caused by developmental ethanol exposure. I will study this using a Caenorhabditis elegans model of FASD. C. elegans is a nematode model system, cultured on agar and fed on a benign strain of bacteria in the laboratory. It develops from a fertilized egg to self-fertilizing adult within 3 days, providing a rapid and cost-effective system for collecting a large genetically identical population raised under homogenous environmental conditions. I previously found that 93% of the C. elegans exposed to ethanol during embryogenesis showed similar magnitude of growth retardation, but 5% of the population showed no growth retardation, and 2-3% of the population showed severe growth retardation. I will investigate the difference in gene expression patterns between groups showing different magnitudes of growth retardation, and pinpoint specific genes responsible for the severity of growth retardation following embryonic ethanol exposure. This project will provide a database of embryonic ethanol response genes, and provide a framework for the development of personalized gene therapy for FASD affected individual who exhibits different types and severity of symptoms.