Functional Analysis of ASD Risk Genes in Zebrafish
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by marked deficits in social communication and repetitive, restrictive behaviors. Recent large-scale whole-exome sequencing studies have led to the identification of a growing number of genes that are strongly associated with ASD. However, the mechanisms by which the loss of ASD risk gene function affects specific cellular and molecular pathways remain incompletely understood, which limits our ability to develop targeted pharmacological treatments. The goal of our research is to identify potential points of convergence across ASD risk genes in the developing vertebrate brain as a path towards uncovering pharmacological candidates. To accomplish this, we use zebrafish as a model system, given their optical transparency, high tractability, and amenability to high-throughput screens. Using CRISPR/Cas9, we generated zebrafish mutants disrupting 10 high confidence ASD risk genes. We performed pharmaco-behavioral profiling to identify pharmacological compounds that might reverse abnormal sensory processing and arousal behaviors in mutants. To identify alterations in brain circuitry, we are performing whole-brain activity mapping. We characterized the behavioral “fingerprints” of zebrafish ASD risk gene mutants and identified points of convergence and divergence across mutant behavioral profiles. We screened 775 FDA-approved drugs in wild-type fish and are currently using these behavioral profiles to predict and test potential suppressors of mutant behavioral phenotypes. These studies highlight the strength of high-throughput functional screens in zebrafish to identify potential convergent pathways underlying ASD risk genes.
Date: 8 February 2022, 16:00 (Tuesday, 4th week, Hilary 2022)
Venue: Zoom link will be sent via mailing list
Speaker: Dr. Ellen Hoffman (Yale School of Medicine)
Organiser: Cortex Club (University of Oxford)
Organiser contact email address: cortex.club@studentclubs.ox.ac.uk
Host: Cortex Club (University of Oxford)
Part of: Cortex Club - Oxford Neuroscience Society
Booking required?: Not required
Booking url: https://www.cortexclub.com/upcoming-events
Booking email: cortex.club@studentclubs.ox.ac.uk
Audience: Public
Editor: Antara Majumdar