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  Investigating the role of calcitonin in electrophysiological function in cardiomyocytes


   Radcliffe Department of Medicine

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  Dr S Reilly, Assoc Prof Ming Lei  No more applications being accepted  Self-Funded PhD Students Only

About the Project

Calcium [Ca 2+ ] plays a crucial role in electrophysiological function of excitable cells such as cardiomyocytes. Calcitonin is a hormone that regulates calcium homeostasis in the body via binding calcitonin receptor that is expressed in cardiomyocytes.

The overall aim of this project is to elucidate electrophysiological response of murine and human cardiomyocytes to calcitonin and its potential role in arrythmogenesis. Subsequently, activity, RNA and protein expression profile of calcitonin and calcitonin receptor will be assessed in patients with sinus rhythm and with cardiac arrhythmia (e.g. atrial fibrillation). A mouse model with the genetic deletion of calcitonin receptor will be utilised during this study to dissect causal relationship between calcitonin receptor and cardiac electrophysiology further. Part of this project will be investigating structural structure of the calcitonin receptor using X-ray crystallization , and will involve extensive cloning, primer design and routine biochemical assays.

TRAINING OPPORTUNITIES

Electrophysiological techniques (measurement of cell contractility, calcium transients, patch-clamping and optical mapping). Molecular biology techniques (qPCR, immunoblotting, immunoprecipitation, immunostaining, ELISA, cell viability, cell proliferation, etc). Extensive cell culture. In vivo and ex vivo electrophysiological measurements in mice.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.

Generic skills training is offered through the Medical Sciences Division’s Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

The department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.

Funding Notes

Funding for this project is available to basic scientists through the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.

For October 2018 entry, the application deadline is 8th January 2018 at 12 noon (midday).

Please visit our website for more information on how to apply.

References

1 Liang et al. Phase-plate cryo-EM structure of a class B GPCR-G protein complex. Nature 546, 118–123 (01 June 2017) doi:10.1038/nature22327
2 Yamashita et al. Membrane depolarization and intracellular Ca2+ increase caused by high external Ca2+ in a rat calcitonin-secreting cell line. J Physiol. 1990 Dec;431:243-67.

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