Establishing clinically relevant zebrafish animal models to study abnormal retinal development using CRISPR-Cas9 mutagenesis

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The development of CRISPR-Cas9 mutagenesis has revolutionised our ability to study human diseases and create animal models with clear translational potential. In this project, the student will use the most modern mutagenesis techniques to create "humanised" zebrafish models of genetic mutations that affect the visual system. We will model genetic mutations from both our local next generation sequencing studies and the 100,000 genomes project to rapidly characterise the functional impact within a zebrafish model. This will help prioritise pathogenic variants from benign variants and identify impact on known and candidate genes involved in development of the visual system. Structural and functional characterisation of the zebrafish will be achieved using high resolution imaging techniques and state-of-the art visual behavioural and electrophysiological assays. The zebrafish is an ideal model organism due to its ease of genetic manipulation, transparency of embryos and rapid development with robust visual responses similar to humans. Establishment of zebrafish mutant lines will provide the opportunity to subsequently carry out pharmacological assays to trial potential treatments.