PhD Position, Cadby Lab/Whitfield Lab, University of Sheffield, Sheffield, United Kingdom

Fully-funded PhD project opportunity at the University of Sheffield, UK

Design, build and use of a light-sheet microscope for automated imaging of a zebrafish neurological disease model

Supervisors: Professor Ashley Cadby (Department of Physics and Astronomy), Professor Tanya Whitfield (School of Biosciences)

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.

Academic and pastoral support will be provided throughout via an interdisciplinary supervisory team and an established Advisory Programme. The student will join the vibrant research teams of the Cadby and Whitfield labs, and will also join a cohort of students at the Neuroscience Institute in the University of Sheffield.

The varied skills training and experience offered in this project will provide a springboard for numerous career opportunities in optical physics, imaging and image analysis, neuroscience or the pharmaceutical industry.

Please see this link for information on how to apply: https://www.sheffield.ac.uk/postgraduate/phd/apply
Please include the name of your proposed first supervisor and the title of the PhD project within your application.

Interviews will likely be held in April. Students must be able to start by October 2023

Funding notes: EPSRC-funded scholarship: 3.5 years home fees and stipend, and £4500 RTSG (in total). Applications are open to students from both the UK and overseas, though we note that due to funding constraints the availability of positions for students with overseas fee status will be more limited. We anticipate competition for these studentships to be very intense. We would expect applicants to have an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).

Useful links:
https://www.sheffield.ac.uk/physics/people/academic/ashley-cadby
https://www.sheffield.ac.uk/biosciences/people/academic-staff/tanya-whitfield
http://whitfield-lab-news.blogspot.com/
https://www.sheffield.ac.uk/lmf
https://www.sheffield.ac.uk/neuroscience-institute