Dr Mandy Johnstone is a Wellcome Trust Postdoctoral Clinical Fellow and Honorary Consultant Psychiatrist in the University of Edinburgh’s Division of Psychiatry.
Through comparative studies of cellular morphology, neuronal progenitor proliferation and migration, gene expression and synaptic function we aim to gain a greater understanding of the underlying mechanisms of neuropsychiatric disorders.
RARE COPY NUMBER VARIANTS (CNVs) IN NEURODEVELOPMENTAL DISORDERS
Schizophrenia and other neurodevelopmental disorders such as autism spectrum disorder and intellectual difficulties are common conditions whose underlying causes are imperfectly understood. They are known to run in families. Some genetic risk factors, including those affecting DLG2 and the so called DISC1 and NDE1 locus, are sufficient to increase risk of major mental illness in those individuals who carry them. It is also known that abnormalities of brain structure and function are closely linked to these genetic factors.
Yet, the cellular mechanism underlying these abnormalities and clinical disorders are still unclear, largely because the human brain is inaccessible.
Recently however, it has become possible to study brain cells in a dish in the laboratory by reprogramming skin cells — known as fibroblasts — to become pluripotent stem cells, which can then be converted into neural progenitors and brain cells — that is neurons and other neural cell-types.
Through comparative studies of cellular morphology, neuronal progenitor proliferation and migration, gene expression and synaptic function we aim to gain a greater understanding of the underlying mechanisms of these disorders.
Our research focus is to better understand the molecular pathophysiology of neuropsychiatric disorders so that we can develop more effective therapies in future. We are investigating the consequences of rare copy number variants (CNVs) associated with neurodevelopmental disorders, including schizophrenia, autism spectrum disorders and intellectual disability using human induced pluripotent stem cells (hiPSCs) as in vitro models.