Grant: Project Grant

Pluripotent stem cells have the potential to become any cell type in an adult organism including nerve cells. SOX2 is a critical gene in stem cells and is also required for normal brain development and nerve cell regeneration. Mutations outside the SOX2 gene, in specialized DNA sequences called enhancers, can influence when and where the SOX2 gene is turned on in the brain. This aberrant expression of SOX2 can lead to neurodegeneration, epilepsy and, in severe cases, infant death due to brain malformation. Our research team recently discovered new enhancer sequences that turn on the SOX2 gene in stem cells and showed that these sequences influence the production of nerve cell precursors from stem cells. Our current proposal will determine the sequences that are important for the function of these regulatory elements and find new genes which, like SOX2, are critical for nerve cell regeneration. Furthermore, we will identify additional enhancers that regulate the expression of genes in the stem cell compartment of the brain and determine how these enhancers are epigenetically modified during brain development and with ageing. This will allow us to better understand why some people develop neurodegenerative diseases that include epilepsy, multiple sclerosis and Huntington's disease and improve disease diagnosis and treatment using precision medicine approaches.