Dr Emily Brookes

• Enhancer regulation of gene expression
• Cortical development
• Topological genome organisation
• Early life adversity

My lab is interested in understanding the contribution of enhancer elements to neurological development and function. We apply molecular biology, imaging, and in vivo techniques in human and mouse model systems to characterise novel enhancers and explore their contribution to gene regulation, neuronal development, and neurological disease. We are fascinated by the topological changes that enable enhancer function, from DNA looping to movement of loci within the 3D nuclear space.

One line of research focuses on the important neurotrophin-encoding gene Bdnf, for which we identified a novel enhancer which promotes the expression of Bdnf transcript variants during mouse neuronal differentiation and activity. Following Bdnf activation, enhancer-promoter contacts increase, and the region moves away from the repressive nuclear periphery. Bdnf enhancer activity is necessary for dendritogenesis in vitro, and for cortical development in vivo. We are researching whether this enhancer is conserved in humans, and its contribution to neurodevelopmental disorders including Rett syndrome.

My lab also investigates the effect of the environment on enhancer function and genome organisation, with a focus on changes that prime states of neurological vulnerability. Stressful events in the postnatal period, known as Early Life Adversity (ELA), are an important predictor of later neuropsychological disorders, including depression and schizophrenia. It is not well understood how these changes are instigated, or how they can be manipulated. Epigenetic regulation is a key facet of environmental influence over expression states. Research has focused on understanding epigenetic changes at genes, but distal enhancers which loop to promoters to promote their expression are a key component of gene regulation. Unbiased screening and follow-on studies will elucidate epigenetic mechanisms through which ELA leads to neurological sensitivity, and the influence of environmental interventions.