Medicine: Swansea University Research Excellence Scholarship: Elucidation of the Molecular Mechanism Underlying Ryanodine Receptor Channel Dysfunction

Closing date: 22 January 2018

Key Information

Swansea University Research Excellence Scholarships (SURES)

Swansea University is proud to offer 15 fully-funded PhD scholarships for students commencing study in October 2018 or January 2019.

The scholarships will be awarded on the basis of student excellence across a portfolio of 34 potential projects.

Project title: Elucidation of the molecular mechanism underlying ryanodine receptor channel dysfunction in sudden cardiac death

Start date: October 2018

The ryanodine receptor (RyR2) is the largest known ion channel, composed of four identical subunits comprising ~5,000 amino acids each. RyR2 mediates intracellular Ca2+ release that is critical for myocardium contraction and reliable heartbeat. Abnormal RyR2 function results in triggered arrhythmias leading to sudden cardiac death. Numerous autosomal dominant, missense mutations in the RyR2 gene are linked with arrhythmogenic cardiac disorders and estimated to affect 1:10,000 people. Normal RyR2 channel regulation is primarily governed by the N-terminus domain, which is involved in two interfaces, one with a neighbouring subunit N-terminus, the other one with the C-terminal pore domain.

Our hypothesis is that RyR2 mutations disrupt inter-domain communication resulting in aberrant Ca2+ release. This PhD project shall therefore enable elucidation of the molecular mechanism underlying the dysregulation of the RyR2 channel in inherited arrhythmogenic cardiac disease. Hence, the new findings from this study may help to indicate effective strategies to prevent deleterious cardiac arrhythmias by restoring normal RyR2 channel function through stabilisation of defective inter-domain interactions.

The prospective student will receive comprehensive training and develop transferable skills in a range of experimental techniques including molecular biology (PCR, generation of recombinant plasmid DNA, site-directed mutagenesis), biochemistry (differential and density gradient centrifugation, protein purification, Western blotting, chemical cross-linking, co-immunoprecipitation), cellular biology (mammalian cell culture, transfection), confocal microscopy (immunocytochemistry, live-cell Ca2+ imaging) and electrophysiology (single channel recordings). They will join a multi-discipline and leading international group for the study of the RyR2 calcium release channel and its role in arrhythmias and sudden cardiac death.

Supervisors / Academic Contacts: Dr Spyridon Zisimopoulos / Dr David Edwards

The successful applicant will have access to our Postgraduate Research Student Training programmes.

Eligibility

Candidates should have (or expect to obtain) a first class honours degree (or equivalent) and/or a master's degree with distinction in a related discipline.

Due to funding restrictions, this scholarship is open to UK/EU candidates only.

Funding

The scholarship covers the full cost of UK/EU tuition fees and an annual stipend of £14,553 for 3 years. 

There will also be £1,000 per annum available for research expenses such as travel, accommodation, field trips and conference attendance.

How to Apply

To apply please complete and return the following documents to Dr Vivienne Jenkins (pgrsures@swansea.ac.uk) quoting reference SUMS4:

Student applications will be evaluated against the following criteria:

  • Literary and Academic attainments (60%)
  • Demonstrable esteem indicators i.e. ambassadorial skills, instincts and opportunities to demonstrate leadership, experience and interest in extracurricular and community activities (40%)

Informal enquiries before the deadline are welcome and should be directed to Dr Spyros Zissimopoulos (spyros.zissimopoulos@swansea.ac.uk / +44 (0)1792 513440).