Due to its immunogenicity in mice and humans the Fluc system does not currently fulfil its true potential in biomedical research. Most BLI studies lack biological relevance and therefore have reduced statistical power, which could be dramatically increased by reporter engineering of the Fluc system. We - and others have heavily engineered the Fluc system for improved in vivo imaging properties. Our infra-luciferin system is unique and helps overcome problems with the validity of BLI in biomedical research by providing more accurate near-infrared cell imaging. However, to date, there has been no attempt to engineer Flucs that better shielded from murine immune system. Since this aim would lead to a reduction in animal use it would fit well with the ‘imaging bioengineered tissues’ theme within the NC3Rs and in-line with the aims of Cardiff University. This work would impact on NC3Rs in 2 ways: a. by improving the uptake of, and extending the use of BLI technologies in stem cell research, and b. by improving the biological relevance and informativeness of stem cell research, hence improving the link between preclinical testing and clinical application of stem cell therapy. Improved translation will lead impact on prevention, diagnosis and treatment strategies in humans and lead to refinement and reduction in the use of small and large animals in wide-ranging research, from the scale of individual experiments to larger scale scientific planning and longer term directions in biomedical and biological sciences.
We seek a motivated PhD student for an exciting project at the Cardiff University School of Biosciences under Profs. Jim Murray and Paul Kemp. The student will engineer novel immune-shielded genetic reporters for in vivo bioluminescence imaging (BLI) of induced pluripotent stem cells using our recently acquired PhotonIMAGER Optima (Biospace Labs, Paris, France).
BLI allows us to answer complex scientific questions in the context of living organisms and refines and reduces animal use in biomedical research. However, issues with safety of Fluc restrict more widespread implementation of BLI and include the requirement for engineering of Flucs ‘that elicit minimal or zero immunogenic response, enhance transfection stability and minimize potential interference of the stem cell function and differentiation.’ (Zhang and Wu. 2007. J. Nucl. Med. 48: 1916–19).
Start date: 1st April 2016.
Academic eligibility requirements: upper second class UK honours degree/equivalent in a relevant subject.
English Language requirements: IELTS with overall score of 6.5 and minimum score of 5.5 in each skill area (or equivalent qualification)
To apply please send a CV and covering letter to Dr. Amit Jathoul: [email protected]
This three year studentship funded by the National Council for the Refinement, Replacement and Reduction (NC3Rs) of animal use provides UK/EU tuition fees and an annual stipend of at least £14,057. To be eligible for fees and stipend applicants must be a UK national/ EU national who has been resident in the UK for three years prior to the programme start. EU nationals who have not been resident in the UK for three years are eligible for fees only provided they have been resident in the EU for three years prior to the programme start.