Over 30% of gene mutations that cause severe autism and intellectual disability with high penetrance in the human population are in genes that encode chromatin modifying or remodelling factors. The Basson lab is interested in understanding how these mutations cause neurodevelopmental disorders. We primarily use mouse models to study how these factors control brain development and function.
Our primary focus at the moment is on factors that either methylate (me) chromatin at a specific amino acid residue (K4) on histone 3 (H3), or factors that “read” these H3K4me modifications and are recruited to H3K4-modified sites in the genome. These factors are implicated in a range of neurodevelopmental disorders, which include CHARGE syndrome, caused by CHD7 mutations, autism and intellectual disability (CHD8, KMT2A, KDM5B), Kabuki syndrome (KMT2D, KDM6A), developmental delay (KDM5B) and schizophrenia (KMT2D). We also work closely with clinical geneticists to identify and characterise new genes associated with these disorders, as well as those specifically associated with cerebellar defects (PRDM13).
Finally, deregulation of chromatin is also associated with age-associated cognitive decline and dementia. We are therefore studying these mechanisms throughout the life course to understand how chromatin abnormalities can cause intellectual disability and cognitive decline with ageing.
Our long-term goals is to provide fundamental insights into the epigenetic mechanisms that underlie neurodevelopmental disorders and cognitive decline and to ask if targeting these mechanisms can provide novel therapeutic possibilities.