Abstract

Research in my lab at the University of Cape Town (UCT) focuses on exploring gene expression in the vertebrate nervous system. We work on diverse models, from lamprey to chicken to human, with the aim of exploring the gene regulatory dynamics that guide cellular development and maturation. My post-doctoral research focussed on the evolution of the neural crest (NC): a vertebrate-specific population of cells that develops in association with the neural tube and contributes to diverse cell types, including the nerves and glia of the peripheral nervous system. I used bulk RNA -seq and ATAC -seq to explore the dynamics of gene expression and regulation in dissected lamprey NC. I identified an enhancer for a key NC regulator, SoxE1, and showed that this lamprey enhancer activity is conserved in gnathostomes. In my lab at UCT we have now narrowed down the functional region of this conserved enhancer using enhancer-reporter assays in both lamprey and chicken embryos. We are have also expanded our investigations of lamprey NC development to include single cell transcriptomic analysis of the pre-migratory NC, revealing sub-populations of NC cells at various stages of development. My lab is now expanding this single-cell approach to investigate gene expression during human brain maturation. Through a collaboration with local neurosurgeons, we have built a biobank of brain tissue collected during elective surgeries to treat epilepsy. Using single nucleus RNA -seq in combination with spatial transcriptomics and bulk ATAC -seq, we are describing the cell atlas of the paediatric brain. By examining the dynamics of gene expression and gene regulation from childhood through to adulthood, we hope to reveal the cell type-specific molecular mechanisms that contribute to human brain maturation.