Grant: Operating Grant

Neurodevelopmental disorders are multifaceted conditions characterized by impairments in cognition, communication, behaviour, and/or motor skills that arise as a result of abnormal brain development. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), intellectual disability, autism and schizophrenia are all neurodevelopmental disorders that share key characteristics and lack precise boundaries. This is further supported by the observed overlap in genes associated with these three disorders and the fact that these disorders converge on common molecular pathways. In this proposal we look at two enzymatic proteins that have been implicated, together with their substrates, in one or more of these neurodevelopmental diseases. Understanding the cellular and molecular mechanisms by which these enzymatic proteins regulate the development of neural circuits is required to better understand the aetiology of neurodevelopmental diseases. Our central hypothesis is that these enzymatic proteins play key roles in the development of neural circuits and that disrupting the proper functioning of these proteins leads to aberrant neuronal connectivity that mimics the neuropathology observed in schizophrenia, autism and/or intellectual disease.