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Biopsychology Colloquium: Investigating functions of human disease genes using C. elegans

Catharine Rankin, Professor, Department of Psychology, University of British Columbia, Vancouver
Tuesday, January 19, 2021
12:00-1:00 PM
Two major challenges facing the genetics of Autism Spectrum Disorders (ASD) are: 1) the large and growing number of candidate risk genes with poorly characterized biological functions and 2) determining whether phenotypic disruptions in these new risk genes are reversible after development. Here, we developed a pipeline to discover functions of ASD-associated genes by inactivating each gene in the model organism Caenorhabditis elegans and observing the phenotypic consequences using machine vision. We quantified 26 phenotypes spanning morphology, locomotion, tactile sensitivity, and learning in >27,000 animals representing 135 genotypes, allowing us to identify disruptions in habituation (a neural circuits plastic ability to decrease responding to repeated sensory stimuli) as a shared impairment. Next, we used CRISPR-Cas9 auxin inducible degradation to determine that habituation impairments caused by developmental loss of the sole C. elegans ortholog of vertebrate neuroligins can be reversed by adult-specific re-expression. We are now using this phenotypic database to rapidly test whether phenotypic disruptions in several other ASD-associated genes are reversible in adulthood. This work charts the phenotypic landscape of ASD-associated genes and will prioritize reversible candidates for further study and therapeutic development.
Building: Off Campus Location
Location: Virtual
Event Type: Presentation
Tags: colloquium
Source: Happening @ Michigan from Department of Psychology, Biopsychology