The development of light sheet microscopy for automated sorting of zebrafish embryos

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Light-sheet fluorescence microscopy is a minimally-invasive imaging technique that can be used to observe living embryos as they develop. The aim of this PhD project is to design and build a light-sheet fluorescence microscope that is compatible with an automated whole-embryo sorting apparatus. The goal is to achieve improved throughput and standardisation of imaging of zebrafish embryos, with wide-ranging applications for the analysis of embryonic mutant phenotypes and for the analysis of drug screening experiments.As a proof-of-principle, imaging will be carried out on zebrafish embryos that have been engineered to carry human disease-causing genetic variants of an adhesion G protein-coupled receptor (aGPCR) gene, adgrg6 (also known as gpr126). The successful student will use transgenic fluorescent markers to highlight neurons and glia to study the development and regeneration of the nervous system in wild-type and adgrg6 mutant embryos. They will also be able to test the effects of rescuing or antagonist small molecules, identified through drug screens, on the developing embryo and the Adgrg6 signalling pathway.This exciting interdisciplinary project combines optical physics, developmental biology, pharmacology, and molecular and genetic approaches. The student will spend the first year designing and building the microscope, gaining training and skills in the use of lasers, lenses and cameras to develop a bespoke imaging platform. The microscope will be housed in the University's Wolfson Light Microscopy Facility, which provides a whole suite of high-resolution instruments for biological imaging. The student will also gain experience in working with zebrafish embryos, and in the use of high-content image analysis techniques. There will be ample opportunity to contribute to experimental design, and to gain skills and experience in presentation, teaching and outreach.