PhD Studentship: Advancing transgenic zebrafish bioassays for drug analysis using imaging, Biosciences

University of Exeter - College of Life and Environmental Science

Academic Supervisors:
Professor Charles Tyler, University of Exeter
Dr Stewart Owen, AstraZeneca

Project Background:

Existing collaborations with the University of Exeter, funded by BBSRC and AstraZeneca, are developing in-life models using various transgenic fish lines. These are used to identify pharmaceutically active chemicals that may cause adverse effects to humans and/or the environment; such as endocrine disruption or oxidative stress; earlier in the product discovery and development process. Here, it is critical to be able to identify products with these properties at the earliest stage before significant investments are made in their further development. The combination of transparent transgenic zebrafish with advanced imaging methods allow for the non-invasive visualising of responses to chemicals, including drugs, in live fish in real time, which offers exciting opportunities for truly advancing our understanding of how chemicals work in the body.  However, these assays require the use of advanced imaging and image processing to maximise the benefits from this research.

The aim of this PhD studentship is to optimise  the use of imaging approaches to better exploit the advantages of our transgenic zebrafish models, and to advance our ability to better understand the effects that chemicals may have on fish (and by extrapolation to mammalian) health. At Exeter we hold an exciting array of transgenic fish for this work including models for oestrogens, oxidative stress, immune function, and neural function amongst others and the model choices will depend on the drugs/chemical investigated. In this project the student will seek to develop imaging approaches that will allow accurate location of a specific tissue or region (e.g. brain, heart, liver, hair cell, gut etc.) within the zebrafish, delineate this chosen target from a complex background and quantify the signal and/or morphology in transgenically modified animal. 

The student will work under the supervision of Prof Tyler and Dr Hetheridge, with supporting expertise from an extensive team of researchers at Exeter working in imaging, image analysis, transgenic fish, and ecotoxicology. The student will also have direct support from a pharmaceutical company, AstraZeneca, with regular short research placements with them. The student will have access to exceptionally facilities for all aspects of this project including: in-life fish exposures, molecular biology, imaging (including Confocal and possibly light-sheet microscopy, mass spec imaging) and advanced image analysis, and will receive multidisciplinary training in techniques spanning molecular biology, bioinformatics, immunology, toxicology and tissue imaging. (S)he will thus develop a valuable set of technical and theoretical expertise that will boost a successful career as an independent scientist.              

The studentship will cover a stipend at the minimum Research Council rate, currently £14,553 per annum, research costs and tuition fees at the UK/EU rate for students who meet the residency requirements outlined by the BBSRC.  Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award but no stipend.  Applicants who are classed as International for tuition fee purposes are not eligible for funding. 

The studentship will be awarded on the basis of merit for 3.5 years of full-time study to commence in January 2018 and is subject to confirmation of funding.  

Applicants for this studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in biology, biochemistry or molecular biology.

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South West England