EASTBIO Immune-neuro interactions in regenerative neurogenesis in zebrafish

Zebrafish, in contrast to mammals, are capable of recovering from spinal cord injury. Spinal cord regeneration in zebrafish involves reactivation of spinal progenitor cells, which generate neurons that integrate into the repaired network. It is important to understand which signals re-program the progenitor cells for regeneration. We have recently shown that the immune system is important for regenerative neurogenesis (Tsarouchas et al., 2018, Nat Commun; 9(1):4670; Caldwell et al, 2019, J Neurosci, 39(24):4694-4713), but how immune cells communicate with neural progenitor cells is largely unknown. The PhD student will generate and analyse data from single cell RNA sequencing of the injured spinal cord and the activated immune cells to find candidate signalling molecules from immune cells that may activate neural progenitor cells. We have already performed preliminary experiments that highlight signal/receptor pairs that may regulate regenerative neurogenesis. These and new ones from additional single cell sequencing will be analysed using CRISPR/Cas9-mediated knock outs of the genes in question, followed by histological and behavioural analyses. This will indicate novel ligand receptor interactions that may ultimately contribute to therapeutic strategies for non-regenerating mammals.

This is an exciting time to join the Becker group, as we have cutting-edge and powerful methods, such as single cell RNA sequencing (in collaboration with Neil Henderson’s group), and CRISPR/Cas9 technology available to dissect the regeneration process. The student will be trained in Bioinformatics, zebrafish handling, quantitative PCR, targeted gene editing, immunohistochemistry and behavioural analyses.