OxTalks will soon move to the new Halo platform and will become 'Oxford Events.' There will be a need for an OxTalks freeze. This was previously planned for Friday 14th November – a new date will be shared as soon as it is available (full details will be available on the Staff Gateway).
In the meantime, the OxTalks site will remain active and events will continue to be published.
If staff have any questions about the Oxford Events launch, please contact halo@digital.ox.ac.uk
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.