Developing drug screening methods on a zebrafish model of motor neurone disease

The FUS protein is a nuclear DNA/RNA binding protein that regulates gene expression and that when mutations occur in this protein it can aggregate and contribute to MND pathology. This project aimed to test the effect of treating transgenic zebrafish larvae expressing mutant FUS-R521C-GFP protein with drugs that induce the autophagy pathway. Different methodologies were used to examine whether these drugs can aid removal of FUS aggregates and decrease levels of mutant FUS protein. Treatments with spermidine saw a decrease in FUS-R521C-GFP protein with western blot analysis and a decrease in aggregation with flow cytometry analysis.