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  How do sex hormones regulate the function of arteries and valves?


   College of Medicine and Veterinary Medicine

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  Dr V MacRae, Dr P Hadoke  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Heart disease and strokes affect about one person in three and are in part caused by arteries and valves becoming stiffened with calcium deposits (1). However, how this occurs and why heart disease is more prevalent among men is not fully known.

Recent studies by our research group (2,3) have shown that testosterone causes the muscle cells found normally in the walls of arteries to partially transform themselves into bone cells and lay down deposits of calcium salts similar to the substances found in the skeleton. The overall result is a thickening and stiffening of the artery wall and a higher risk for heart disease.

This project will assess the influence of oestrogen and testosterone on artery and valve development and function. It will utilise in vitro culture models of vascular cells and develop new in vivo mouse models of arterial and valve calcification. Studies will involve the assessment of calcification in vitro and in vivo through the quantification of calcium and phosphate deposition using biochemical assays and fluorescent probes. This will include the development of novel in vivo imaging protocols using state-of-the-art PET/computed tomography (CT) scanning, a technique currently used to assess calcification in patients. We will also use our models of vascular calcification to investigate the role of different pathways that may be regulated by sex hormones during the calcification process; for example Wnt signalling and autophagy. In addition, RNAseq with subsequent informatics analysis will be undertaken to identify novel underpinning mechanisms. Techniques used will include histology, qPCR, western blotting, immunofluorescent staining and siRNA knockdown.

The student will be encouraged to present their work at International and European scientific conferences and will have the opportunity to undertake a scientific exchange visit with The University of Hawaii, USA.

Application procedures
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University’s on-line application system for September 2018 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=829

Applicants for the Principal’s career development studentship must also complete the specific on-line application form.

Applicants for an Enlightenment Scholarship must also complete the specific on-line application form.
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 16th January 2018

Funding Notes

This project is eligible for a University of Edinburgh 3-year PhD studentship or Principal's Career Development Studentship. (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/uk-eu/university-scholarships/development) or a 4-year Enlightenment Scholarships (https://www.ed.ac.uk/student-funding/postgraduate/uk-eu/university-scholarships/enlightenment )

International students applying for a 3-year PhD studentship or Principal's Career Development Studentship should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research). International students applying for an Enlightenment Scholarship should note that tuition fees are included in the award and an Edinburgh Global Research Studentship is not required.

References

1. Zhu D, Mackenzie NC, Farquharson C, MacRae VE 2012 Mechanisms and clinical consequences of vascular calcification. Front Endocrinol. 3:95.
2. Zhu D, Hadoke PW, Wu J, Vesey AT, Lerman DA, Dweck MR, Newby DE, Smith LB, MacRae VE 2016 Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification. Sci Rep 6:24807.
3. www.thenakedscientists.com/articles/interviews/why-do-men-have-more-heart-attacks

Where will I study?