How does our genome regulate the process of development and cell-type specialisation? Specific genes are expressed at discrete times due to the activation or repression of DNA regulatory regions. Our research investigates how the genome functions in stem cells to regulate self-renewal and differentiation. We often think about transcription as occurring on a particular gene in a linear manner whereas the nucleus is a three dimension organelle into which the genome is folded and organised. Within this folded structure DNA regulatory sequences physically contact the genes they regulate forming tissue-specific chromatin loops.
We use CRISPR Genome Editing, Molecular Biology and Cellular Imaging techniques combined with Genome-Wide Sequencing approaches and Bioinformatics analysis to investigate the mechanisms that underlie tissue-specific regulation of gene expression and genome folding. Our previous work has identified the enhancers that activate numerous genes in stem cells including a distal enhancer of the Sox2 transcription factor which is required to maintain the stem cell state. The work we do provides a deeper understanding of how our DNA makes us unique and predisposes us to particular diseases. Our work also identifies new ways to consider treating genetic diseases with CRISPR Genome or Epigenome Editing.