Human skin depends on systemic provision of fatty acids that are important to maintain the integrity of the epidermal barrier as well as to support the associated immune and inflammatory reactions. Polyunsaturated fatty acids (PUFA) are of particular importance for healthy human skin, as they mediate many biological processes. PUFA act through modifying cellular membrane composition, altering gene and protein expression, mediating signalling events and affecting the production of bioactive lipid mediators.
Although dietary supplementation with oils containing anti-inflammatory n-3PUFA has shown promising results in conditions such as psoriasis, sunburn inflammation and cutaneous wound healing, there are many unanswered questions related to their mode of action. Some of these interesting questions include the nature of bioactive lipids formed by human skin cells, their biological activities and impact on the quality of the epidermal barrier, the way they interact with drugs and food ingredients, their influence on the cutaneous microbiome, and how they respond to environmental factors such as sunlight.
In this project we will use skin cells grown in culture as well as a human skin organ culture model. Tissue and cells will be challenged with known irritants, allergens and other stimuli. Skin lipids will be profiled with state-of-the-art mass spectrometry based lipidomics and bioinformatics will be used to review the large data sets produced by this technology. The bioactivity of the lipid mediators identified will be assessed using a range of cell-based assays, while lipid metabolising enzyme expression will be assessed by western analysis, immunohistochemistry, FACS and PCR.
The outcome of these investigations will generate new information including the identification of lipid species with protective bioactivities that can improve skin health. Furthermore, the project has great potential to interrogate the role of nutrition for skin health and support the development of a systems approach to skin biology.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a Biomedical Sciences, Biochemistry, Pharmacology or one of the medical/health sciences. A Masters qualification in a similar area would be an advantage.
Candidates with experience or an interest in Bioanalysis are encouraged to apply.
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/
). Informal enquiries may be made directly to the primary supervisor.
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
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.
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. El Chami C, Haslam I, Steward M and O’Neill CA (2018) Organic osmolytes preserve the function of the developing tight junction in ultra violet B irradiated rat epidermal keratinocytes . Sci Rep 8(1):5167
5. Alhasaniah A, Sherrat, M and O’Neill CA (2018) ‘The impact of ultraviolet radiation on barrier function in human skin: Molecular mechanisms and topical therapeutics. Curr Med Chem. In press.
6. Sultanna R, McBain A and O’Neill CA (2013) Lysates of lactobacillus and Bifidobacterium augment tight junction barrier function in human primary epidermal keratinocytes in a strain dependent manner. Appl. Environ, Microbiol. 79(16) 4887-4894