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Developing a novel platform to map endogenous gene expression in vivo for correlation to life course heart health in murine models

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  • Full or part time
    Prof A Fisher
    Prof Paul French
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Imperial College London’s BHF Centre of Research Excellence, sponsored by the UK’s leading charity for pioneering research into heart disease, is an established cross-disciplinary venture. Our aim has been to foster a unique collaborative research environment that draws on Imperial’s world class reputation in cardiovascular science, engineering and collaborating physical sciences.

Mammalian Utrophin and Dystrophin are paralogous genes that are important for skeletal and cardiac muscle function, but are expressed sequentially during ontogeny. We will study the processes that regulate this switch in gene expression, using new mouse models to image gene expression in development and to profile epigenetic modifications that curtail Utrophin expression. We aim to explore whether epigenetic interventions are useful in Duchenne’s Muscular Dystrophy. Using RT-PCR, bisulphite and RNA sequence analysis we will examine gene expression in muscle samples throughout development, identify critical time points where Utrophin is silenced in favour of Dystrophin, and evaluate chromatin-based changes at the Utrophin locus at these times. We will exploit two new mouse reporter lines where Utrophin and Dystrophin expression can be detected using luciferase and LacZ read-outs, to examine gene expression during development by bioluminescence and photoacoustic imaging and optical projection tomography. This multidisciplinary PhD project based between the MRC-LMS CSC and the Physics Department will include the development and application of methodologies to investigate whether epigenetic drug treatments can be used to prolong the expression of Utrophin into adulthood. It will require expertise in cell culture, animal studies, optical instrumentation and computer-based data analysis.

Imperial College London provides excellent opportunities for research student training. All students benefit from a full programme of training in research and transferable skills organised through the Graduate School, the quality of which has been recognised several times at the Times Higher Education (THE) Awards.

Interviews will be held W/C 25 June at the MRC London Institute of Medical Sciences

Funding Notes

Applications are invited for a 3-year PhD studentship within the BHF Centre of Research Excellence at Imperial College London. The studentship is funded through a training grant from the BHF on a tax-free bursary starting from £22,278 per annum (increasing annually). Tuition fees will be paid at the Home/EU rate. There is no provision for overseas student fees.

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