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Advancing transgenic zebrafish bioassays for drug analysis using imaging, Biosciences - PhD (BBSRC CTP)

  • Full or part time
  • Application Deadline
    Saturday, September 30, 2017
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Existing collaborations with the University of Exeter, funded by BBSRC and AstraZeneca, are developing in-life models using various transgenic fish lines to identify pharmaceutically active chemicals and plant protection products that cause endocrine disruption or oxidative stress earlier in product discovery and development process. Chemicals of this nature are highly regulated by national and international policy-makers, and in the case of endocrine active plant protection products, they are unlikely to gain regulatory approval and reach market. Therefore it is critical for UK competitiveness to be able to identify products with these properties at the earliest stage before significant investments are made in their further development. In recent years there have been significant advances in the development of high throughput screening (HTS) assays to determine the clinical efficacy and safety of medicinal products. Many of these assays are being developed to support mechanistic studies to determine mode of action, measure target organ effects and identify adverse outcome pathways. The requirements for such approaches are: 1) the availability of a robust and characterised model; 2) fluid dynamics or robotic systems for automated sample/tissue/animal handling to present the sample to the imaging platform, (ideally these should be flexible to allow multiple tests systems); and 3) robust, sensitive and efficient automated bioimaging and data processing tools capable of measuring relevant of phenotypic endpoints. The aforementioned collaborations are delivering the characterised models and automated platforms, however a major bottleneck in realising the true potential of these HTS assays is the availability of automated and sophisticated bioimage analysis. This would unlock the potential for mining the information presented in these images, realising high content screening that will enable mechanistic understanding of how and why these compounds effect fish the way they do. This BBSRC Industrial CASE will include the development of bioimage analysis tools to increase both the throughput and content of the samples being bioprocessed centred around the use of transgenic fish.

The aim of this PhD studentship is to combine the use and development of imaging approaches and transgenic zebrafish models to advance our ability to better understand the effects of drugs and other chemicals on fish health. At Exeter we hold an exciting array of transgenic fish for this work including transgenic zebrafish models for oestrogens, oxidative stress, immune function, and neural function and the model choices will depend on the drugs/chemical investigated. In the project the student will seek to develop imaging approaches that will allow for accurately locating a specific tissue or region (e.g. brain, heart, liver, hair cell, gut etc.) within the zebrafish, delineate the specific region or tissue of interest against a complex background, quantify the signal and/or morphology in transgenically modified animal and in specific cases co-locate the specific chemical or metabolite of interest. Considerable background work for this studentship has been conducted at Exeter with a variety of different imaging platforms for enabling this exciting project. The studentship will involve conducting in-life exposures of the various transgenic fish lines to specific drugs and chemicals for the imaging work. There is considerable expertise in imaging and image analysis in the team at Exeter for supporting this work.

For further information please see http://www.exeter.ac.uk/studying/funding/award/?id=2659

Funding Notes

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.

If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.0 in any section by the start of the project. Alternative tests may be acceptable (see View Website).

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