EPSRC Doctoral Training Partnership PhD Studentship 2015

Healthcare Technologies

Faculty of Medical & Human Sciences

Modelling the network of bioactive lipids that mediate cutaneous inflammation

Professor Anna Nicolaou & Professor Rainer Breitling

The objective of this 3.5-year EPSRC-Unilever funded PhD is to develop the first predictive model of the metabolic network of cutaneous inflammatory lipids targeted for the discovery of anti-inflammatories.

The studentship provides full support for tuition fees, a conference/travel allowance and annual minimum tax-free stipend at UK Research Council rates (£14, 057 from 2015/16). Due to commence October 2015, the project is open to UK/EU* nationals only due to the nature of the funding.

Lipids are important for skin biology, contributing to the structure of the epidermal barrier and mediating the development and interactions of various skin cells. They are also intimately involved in the inflammatory response that develops following exposure to environmental factors, such as sunlight, and underpin processes involved in wound healing and cutaneous disease [1]. The cell membrane contains fatty acids that serve as metabolic precursors to bioactive lipids acting as potent mediators of inflammation. Changing the membrane fatty acid composition with nutritional supplements using anti-inflammatory fatty acids can alter the profile of lipid mediators and create a less inflammatory environment that can protect the skin and be beneficial in combating cutaneous disease.

In this project we want to construct a quantitative, predictive computational model of the metabolic network of skin lipids. This model will help us understand the complex interaction of skin fatty acids and their metabolites, and investigate how their altered profiles affect the relationship of epidermal keratinocytes and dermal fibroblasts.

To achieve our objectives we will use mass spectrometry-based skin lipidomics to measure metabolites, and estimate reaction rates and enzyme kinetics [2]. This information on lipid networks will then be processed using a new modelling strategy based on explicit consideration of parameter uncertainty that permits robust predictions [3].

The resulting model will allow further understanding of skin lipid biology, permit mapping of lipid networks contributing to inflammation, and support the design of interventional studies to combat skin disease.

The successful candidate will benefit from extensive training in mass spectrometry-based lipidomics, cell culture, protein analysis, biochemistry and computational modelling of enzyme kinetics.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in chemistry, biochemistry, pharmacy or related area. Previous experience in bioinformatics, modelling, mass spectrometry and/or analytical biochemistry would be an advantage.

Please direct applications in the following format to Professor Anna Nicolaou: (anna.nicolaou<στο>manchester.ac.uk):          

• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.

Applications are invited up to and including Monday 11 May 2015.

www.pharmacy.manchester.ac.uk/staff/anna.nicolaou

www.pharmacy.manchester.ac.uk

www.mib.manchester.ac.uk

*Applicants must be UK/EU nationals who have been resident in the UK for at least three years by 1^stSeptember 2015.

[1]. AC Kendall, A Nicolaou. Bioactive lipid mediators in skin inflammation and immunity (2013) Prog Lipid Res, 52:141-164.

[2]. SA Murphy, A Nicolaou. Lipidomics applications in health, disease and nutrition research (2013) Mol Nutr Food Res  57;1336-46.

[3]. Medema MH, van Raaphorst R, Takano E, Breitling R (2012): Computational tools for the synthetic design of biochemical pathways. Nature Rev. Microbiol. 10:191–202.