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(MRC CASE DTP) Investigating the cutaneous lipidome to understand the molecular basis of photosensitivity disorders

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  • Full or part time
    Prof A Nicolaou
    Prof L Rhodes
    Dr A Kendall
    Dr M Farrar
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

While healthy human skin can handle daily exposure to sunlight for short periods of time, a large number of people show altered sensitivity to solar radiation and develop inflammatory phototoxic skin reactions. These photosensitivity disorders can vary from mild to extremely severe conditions that can greatly affect patients’ lifes. Although photosensitivity can have genetic or immune origins, it can also develop in response to a number of commonly used drugs and food ingredients. Currently, the exact molecular basis for photosensitivity disorders is not clearly understood.

Human skin depends on specialist lipids to maintain its structure and function, with locally produced lipid mediators known to be involved in cutaneous inflammatory and immune reactions, including the skin’s response to sunlight. Here we propose to explore the involvement of skin lipids, collectively known as the ‘cutaneous lipidome’ to understand the molecular basis of photosensitivity disorders. We plan to use clinical material and investigate local dermatological and systemic changes occurring in response to solar radiation. As well as conducting a clinical study, we will use cells and a human skin organ culture model. We will apply mass spectrometry targeted and untargeted lipidomics to study the type and relative abundance of lipids involved in reactions triggered by solar radiation, and will explore their localisation through mass spectrometry lipid imaging. The study outcomes will give us a detailed insight into the attributes of human skin prone to develop abnormal inflammatory reactions. Also, we believe that by comparing changes in the skin and blood of people with differing photosensitivity disorders we will be able to identify biomarkers characteristic of the disease and support decisions on specialist treatments. This is particularly important as, currently, there are no effective treatments for these conditions.

This multidisciplinary project will provide training in biochemistry, analytics, skin biology, pharmaceutics and clinical research, including handling of large data sets generated by lipidomics, cell and organ culture, lipid extractions and mass spectrometry analyses. During their placement, the student will work at Waters’ research laboratories and train in cutting edge mass spectrometry imaging equipment and software.

The student will join a vibrant research environment at the University of Manchester and will work closely with our industrial collaborators at Waters, Wilmslow. This partnership will provide unique interdisciplinary training at the interface of chemistry-biology-medicine, and will give the student unique skills valuable for a career in modern academia and the pharmaceutical industry.

https://www.research.manchester.ac.uk/portal/anna.nicolaou.html

https://www.research.manchester.ac.uk/portal/lesley.e.rhodes.html

Funding Notes

This is a CASE studentship in partnership with Waters Corporation and will be funded under the MRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Supervisor to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found here https://www.bmh.manchester.ac.uk/study/research/mrc-dtp/apply/. Interviews will be held on 25th June.

Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

References

1. AC Kendall, MM Koszyczarek, EA Jones, PJ Hart, M Towers, CEM Griffiths, M Morris, A Nicolaou. Lipidomics for translational skin research: a primer for the uninitiated. (2018) Exp Dermatol (doi: 10.1111/exd.13558).
2. AC Kendall, M Kiezel-Tsugunova, LC Brownbridge, JL Harwood, A Nicolaou. Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model (2017) Biochim Biophys Acta 1859:1679-1689.
3. AC Kendall and A Nicolaou. Bioactive lipid mediators in skin inflammation and immunity (2013) Prog Lipid Res 52; 141-164.
4. Hart PH, Norval M, Byrne SN, Rhodes LE. Exposure to Ultraviolet Radiation in Modulation of Human Diseases (2018) Annu Rev Pathol. In Press.
5. Farrar MD, Nicolaou A, Clarke KA, Mason S, Massey KA, Dew TP, Watson REB, Williamson G, Rhodes LE. A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation (2015) Am J Clin Nutr 102: 608-15.



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