About the Project
A key player in the recognition of DNA methylation is Methyl-CpG Binding Protein 2 (MeCP2). Mutations within MeCP2 lead to the devastating autism spectrum disorder, Rett syndrome. However, the underlying molecular functions of MeCP2 are poorly understood. We therefore developed novel mouse models that recapitulate disease-associated mutations in MeCP2. We found that these mice manifest Rett syndrome-like phenotypes through a loss of MeCP2 binding to methylated DNA and a concomitant reduction in MeCP2 protein stability (Goffin et al, 2012). Additionally, we found that loss of MeCP2 function leads to alterations in neural circuit function in a cell type-dependent manner (Goffin et al, 2014).
This project will build on these findings and provide new insights into the mechanisms through which DNA methylation and its recognition by MeCP2 plays in regulating proper neuronal function. This project will employ cutting edge genetic and electrophysiological techniques and is ideal for students with an interest in mechanisms underpinning health and disease.
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