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  Vitamin D3 – a novel anti-inflammatory for treatment and prevention of eye disease (RDF17-R/APP/MCDERMOTT)


   Faculty of Health and Life Sciences

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  Prof A McDermott  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The cornea is the transparent window that allows light in to the eye for vision. It is essential that the cornea has robust immune and inflammatory responses to protect itself, however, these responses are commonly “a double edged sword” meaning that while they are generally beneficial they often also have harmful effects. This is of particular concern in the cornea since excessive, unregulated inflammation significantly compromises vision. Inflammation is a major contributor to the pathogenesis of several common eye conditions such as dry eye, infection, and the inability to tolerate contact lenses.

Cytokines are major inducers of ocular inflammation. Previously we observed that Vitamin D3 significantly attenuates TLR agonist stimulated cytokine production. This suggests that Vitamin D3, which is synthesized locally in the eye, may act as an endogenous anti-inflammatory and has potential as a novel pharmaceutical. The overall goals of this project are to investigate how Vitamin D3 suppresses inflammatory responses in the eye and to translate this knowledge into the development of novel pharmaceuticals for the treatment and prevention of ocular inflammation. Specific questions to be addressed include: determining the molecular mechanism through which Vitamin D3 inhibits TLR induced cytokine production by studying modulation of TLR expression and activation; determining if Vitamin D3 can suppress inflammation induced by other pattern recognition receptors; comparing the effects of Vitamin D3 analogues to determine which has the optimal anti-inflammatory activity.

The studies will utilize corneal epithelial cells in conventional monolayer culture as well as in a unique 3D culture system that mimics the ocular environment, particularly the blinking of the eyelids. The PhD student will learn a variety of cellular and molecular techniques in a supportive environment that fosters independent critical thinking and will be encouraged to develop “maker” skills, attend and present at conferences and publish scientific manuscripts.

Eligibility and How to Apply
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required (evidence required by 1 August 2017).

For further details of how to apply, entry requirements and the application form, see:
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please ensure you quote the advert reference above on your application form.
Start Date: 2 October 2017

Northumbria University is an equal opportunities provider and in welcoming applications for studentships from all sectors of the community we strongly encourage applications from women and under-represented groups.

Funding Notes

This project is being considered for funding in competition with other projects, through one of two types of funding packages available:
• Fully funded studentships include a full stipend, paid for three years at RCUK rates (for 2017/18 this is £14,553 pa) and fees (Home/EU £4,350 / International £13,000 / International Lab-based £16,000), and are available to applicants worldwide.
• As Northumbria celebrates its 25th anniversary as a University and in line with our international outlook, some projects may also be offered to students from outside of the EU supported by a half-fee reduction.


References

Reins R, Mesmar F, Williams C, McDermott AM. (2016) Vitamin D induces global gene transcription in human corneal epithelial cells: Implications for corneal inflammation. Invest Ophthalmol Vis Sci 57, 2689-2698.

Reins R, Hanlon SD, Magadi S, McDermott AM. (2016) Effects of topically applied Vitamin D during corneal wound healing. PLoS One 11:e0152889.

Reins RY, Baidouri H, McDermott AM (2015) Vitamin D activation and function in human corneal epithelial cells during TLR-induced inflammation. Invest Ophthalmol Vis Sci 56, 7715-7727.

Reins RY, McDermott AM. (2015) Vitamin D: Implications for ocular disease and therapeutic potential. Exp Eye Res 134, 101-110.

Where will I study?