(BBSRC CASE DTP) Investigating the cutaneous lipidome to understand how skin responds to sunlight exposure
Prof A Nicolaou
Dr Sam Butterworth
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Background: The ultraviolet radiation (UVR) component of sunlight penetrates the skin layers and can modify the lipid component of the epidermal barrier. This effect results in the activation of biochemical pathways that control production of bioactive lipids that mediate inflammation and immunity, but can also lead to the modification of structural lipids and their accumulation in cellular membranes. These changes can then modulate various immune responses in the skin. While some of these UVR-induced changes in skin lipids are reversible and form part of the inflammatory response and its resolution, others may have longer lasting effects and influence skin physiology.
Aim: We want to explore the UVR-induced changes in skin lipids as means of understanding the normal physiology of human skin when exposed to sunlight, and appreciate the role of lipids in maintaining skin health. We will then use this information to understand how human skin reacts with xenobiotics that interact with sunlight and, this way, support the design of studies for the development of pharmaceuticals. Overall, the project will allow detailed study and understanding of the skin lipidome and perturbations induced by sunlight and xenobiotics, permit mapping of lipid networks contributing to inflammatory responses and inform research into human health.
Experimental: We will use 3D human skin models, primary skin cells in culture, and human skin in organ culture. We will then employ mass spectrometry-based assays and lipid imaging to assess changes in the various types of skin lipids and their accumulation in cell membranes.
Training: The project will provide training in multiple disciplines (biochemistry, analytics, pharmaceutics, biology) including the handling of large data sets generated by lipidomics. While at UoM, the student will train in cell and organ culture, lipid extractions and analyses by mass spectrometry (triple quadrupole and time-of-flight coupled to liquid and supercritical fluid chromatography), and data processing. During the placement periods, the student will learn the requirements of drug development and how skin physiology and photo reactivity can inform drug discovery. The student will also have access to AstraZeneca’s research into microphysiological systems and 3D cell models that will be used to investigate aspects of normal skin functioning, and will work with AstraZeneca’s world leading mass spectrometry imaging group to investigate novel ways to detect changes in the lipidome.
Research Environment: The student will join a vibrant research environment at the Laboratory for Lipidomics and Lipid Biology, University of Manchester and will work closely with our industrial collaborators at AstraZeneca, Cambridge. This partnership will provide unique interdisciplinary training at the interface of chemistry-biology, and will give the student unique skills valuable for a career in modern academia and pharmaceutical industry.
This is a CASE studentship is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange 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 on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
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.
1. AC Kendall and A Nicolaou. Bioactive lipid mediators in skin inflammation and immunity (2013) Prog Lipid Res 52; 141-164.
2. AC Kendall, SM Pilkington, KA Massey, G Sassano, LE Rhodes, A Nicolaou. Cutaneous distribution of bioactive lipid mediators of inflammation (2015) J Invest Dermatol 135; 1510-1520.
3. G Astarita, AC Kendal, EA Dennis, A Nicolaou. Targeted lipidomic strategies for oxygenated metabolites of polyunsaturated fatty acids (2015) Biochim Biophys Acta 1851; 456-468.