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Targeting the Synaptic Pathway in Neurodevelopmental and Psychiatric Disorders

Principal Investigator:
  • Ann Marie Craig,

    University of British Columbia

Team Members:
  • Michael Gordon, Brain Research Centre, University of British Columbia
  • Tim Murphy, University of British Columbia
  • Richard Brown, Dalhousie University
  • Genome BC
  • University of British Columbia
  • The Djavad Mowafaghian Centre for Brain Health
  • Vancouver Coastal Health

Project Overview

Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social interaction, poor communication, and restricted, stereotyped patterns of behavior. Autism and schizophrenia affect over 1% of the population, and each has strong genetic associations with 60-90% heritability among twins. Recent research identified mutations in a shared genetic pathway in autism and schizophrenia, in genes that function to build synaptic connections between nerve cells, specifically in neurexin cell adhesion proteins and partners linked in a biochemical pathway. Mice with autism-associated mutations in neurexin pathway genes exhibit impaired social interactions and have been developed as single-gene models for exploring and treating autism. In this project, Dr. Craig and her team are studying the fundamental properties of the neurexin synaptic pathway in cell culture and animal models of autism. They are using state of the art biochemical, structural, fluorescence imaging, and behavioral assays in both fly and mouse models based on the human genetics to better understand the subtle differences in brain organization and function that occur in these neuropsychiatric disorders. They have discovered novel regulatory mechanisms of the neurexin pathway and will validate their importance in brain function. A major component of this research will be to test the efficacy of novel therapeutic agents for amelioration of behavioural and cellular phenotypes associated with the devastating consequences of these disorders. The teams hopes that such in-depth molecular studies based on the human genetics will ultimately lead to the most effective therapeutics for autism and schizophrenia.