Grant: Project Grant

Autism Spectrum Disorder (ASD) is a diverse group of genetic neurodevelopmental disorders characterized by social impairment, repetitive behaviour, and sensory processing abnormalities. This disorder affects ~1% of the population, and is often severely debilitating with no broadly successful treatments available. Although a very large number of mutations in many, many genes have been implicated in ASD it is not clear what all of these genes do, how these genes interact, and how the mutations contribute to ASD. I propose using a microscopic round worm, Caenorhabditis elegans to characterize the function ASD-associated genes. C. elegans is cheap and easy to genetically engineer, and our automated behavioural scoring system allows us to rapidly and systematically study neurodevelopmental and behavioural effects of mutations in each of the hundreds of genes associated with ASD. This research will help us understand what these genes do and how they might contribute to ASD. Thus understanding how these genes function in the nervous systems of living animals may shed light on what causes ASD. We will also be able to use the genome-editing tool CRISPR-Cas9 to determine if behavioural abnormalities caused by mutations in a large number of ASD-associated genes are reversible by reintroducing the gene in adulthood. This has been shown for a few ASD-associated genes before, and has offered tremendous hope for families with ASD and is critical for designing treatments. These studies will also allow grouping genes into network that contributing to specific behavioural phenotypes which may allow a greater understanding of the heterogeneous nature of ASD, and identify novel therapeutic targets for treating ASD.