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Effect of vitamin D in vascular and endocrine cells


Faculty of Biology, Medicine and Health

About the Project

Vitamin D3 deficiency is a common public health problem worldwide that is increasingly believed to contribute not only to decreased bone mineralisation but potentially to other serious medical conditions. Interestingly, there is even increasing evidence of links between obesity and vitamin D3 deficiency. However, the mechanisms underlying these associations remain poorly understood. This project will look at the cellular actions of 1,25(OH)2 vitamin D3 formation on vascular cells and on cells of the endocrine system, with particular regard to understanding how the vitamin D signals within the cells. Since chronic kidney disease is associated with low vitamin D levels and life-threatening vascular calcification the project will also look at the role of the vitamin D receptor in smooth muscle cells mineralisation. The techniques involved in this project include hormone assay, live cell calcium imaging, kinase assays and transfection with siRNAs for the selective knockdown of calciotropic signal regulators.

Training/techniques to be provided:

Intracellular signalling measured using a) FRET-based cell imaging and b) Epifluorescence microscopy
Cell culture, transfection, gene knockdown and cell assay. Smooth Muscle Cell mineralisation
Molecular techniques including Immunoblotting, Immunofluorescence, RT-PCR and mutagenesis

Entry Requirements:

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1] Wu-Wong JR (2009) Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. British Journal of Pharmacology 158, 395-412.

[2] Absi M, Ward DT (2013) Increased Endothelin-1 Responsiveness in Human Coronary Artery Smooth Muscle Cells Exposed to 1,25-Dihydroxyvitamin D3. American Journal of Physiology (Cell Physiology). 304, C666-C672.

[3] Campion KL, McCormick WD, Warwicker J, Bin Khayat ME, Atkinson-Dell R, Steward MC, Delbridge LW, Mun H-C, Conigrave AD, Ward DT. (2015) Pathophysiological Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism. Journal of the American Society of Nephrology. 26, 2163-2171.

[4] Binmahfouz LS, Centeno PP, Conigrave AD, Ward DT. (2019) Identification of Serine-875 as an Inhibitory Phosphorylation Site in the Calcium-Sensing Receptor. Molecular Pharmacology. Jun 12. doi: 10.1124/mol.119.116178

[5] Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT (2019) Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635). Journal of Bone & Mineral Research May 7. doi: 10.1002/jbmr.3747

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