PhD Studentship - Influence of PMCA4 Ablation on Vascular Contractility

Faculty of Medical and Human Sciences

University of Manchester

The Cardiovascular Medicine Research Group is inviting applications for a distinguished three-year BHF PhD studentship. The studentship is open to UK/EU nationals only due to the nature of the funding and will attract an annual stipend of £16, 000 in addition to tuition fees. The project is due to commence in September 2008.

To ensure the normal functioning of all parts of the body it is essential that they are supplied with adequate amounts of blood, oxygen and nutrients. Local blood flow is governed largely by the diameter of small blood vessels which are determined by the concentration of calcium within the cells of the vessel wall. The presence of calcium is influenced by the relative activity of pumps which elevate and remove calcium from these cells.

One such pump is the plasma membrane calcium ATPases (PMCA), however, the influence of PMCA on vascular contraction is unclear. This is predominantly because, in addition to their direct effects on calcium homeostasis, PMCAs may have additional roles in signal transduction which may differentially affect contractility.

Using genetically modified mice which are deficient in PMCA4 (the main vascular isoform) this project will investigate for the first time the effects of ablation of PMCA4 on isolated resistance artery contractility. The influence of calcium homeostasis and neuronal nitric oxide synthase (implicated previously as a target for PMCA) in all responses will be studied. The results will help to determine whether PMCA4 would be an appropriate target for therapeutic modulation.

The project has a significant biological science element and will be particularly appropriate for a student with a good first degree or Masters in biomedical or biosciences related subjects, who wishes to use their skills and knowledge in the cardiovascular field. The ideal candidate will also have a strong interest and experience in experimental science.

The project employs a variety of different experimental techniques including pressure myography (to measure contractility) and simultaneous calcium imaging (to monitor changes in calcium inside the smooth muscle cells of the intact arteries). The student will be expected to perform all the experiments associated with the project, will be responsible for data analysis and contribute fully to dissemination of results. Full support and training will be given.

This project will be an excellent grounding for those wishing to pursue a career in cardiovascular sciences.

Interested candidates should submit a CV and detailed covering letter outlining their suitability for the PhD project to Dr Clare Austin at:

clare.austin@manchester.ac.uk.

Contact details for two academic or professional referees should also be provided.

Applications will be welcomed up to and including Monday 14 July 2008.

For further details on the project please contact Dr Austin at the address above.

http://www.medicine.manchester.ac.uk/cardiovascular/