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Developing an in silico model of the cutaneous lipidome


Project Description

Bioactive lipids are key signalling molecules regulating skin health and contributing to the structure and function of the epidermal barrier. They are also important regulators of immune reactions and other interactions taking place between various resident and infiltrating skin cell types. Dysregulation of the cutaneous lipidome can compromise the physical and immunological barrier, so it is important to understand the network of lipids involved in the skin cell signalling system. As the lipid network is complex, with cell-specific lipid profiles and many enzymes involved in their biosynthesis and catabolism, we need to develop novel predictive tools to help us understand and modulate lipidome dynamics in health and disease.

To better dissect the role of lipids in skin cell interactions, we plan to create a quantitative computational model of the lipidome of epidermal keratinocytes, using cutting-edge systems biology methods, based on ensemble models of differential equations. To support the computational model building, we plan to gather lipidomic data from human epidermal keratinocytes and immune cells grown in culture, and use state-off-the art mass spectrometry assays to measure lipids and estimate reaction rates and enzyme kinetics. Additionally, the model will be refined to increase its predictive abilities by integrating proteomics and/or transcriptome dynamic data.

This 4-year PhD provides a unique opportunity to work at the interface of chemistry and biology, in close collaboration with Unilever. The student will join a multidisciplinary team at the University of Manchester with expertise in lipid and skin biology, mass spectrometry, immunology, computational systems biology and postgenomic molecular profiling, and will undertake placements in a UK Unilever R&D lab. This studentship will be provide a unique multi-disciplinary training and will equip the student with a set of skills valuable for a career in modern academia and industry.

Entry Requirements
Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in Chemistry, Biochemistry, Biology or related subject area/discipline. A Masters degree in a relevant subject and/or experience in Computational Biology, Systems Biology, Bioinformatics or Bioanalysis is desirable.

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/). On the online application form select PhD Pharmacy and Pharmaceutical Sciences.

Funding Notes

BBSRC CTP with Unilever. Studentship funding is for a duration of four years to commence in October 2020 and covers UK/EU tuition fees and an annual minimum stipend £16,000 per annum.

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.

References

1. 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
2. AC Kendall, SA Murphy, SM Pilkington, F Del Carratore, AL Sunarwidhi, M Kiezel-Tsugunova, P Urquhart, REB Watson, R Breitling, LE Rhodes, A Nicolaou. Dynamics of the skin mediator lipidome in response to dietary omega-3 fatty acid supplementation (2019) FASEB J 33:13014-13027
3. A Tsigkinopoulou, A Hawari, M Uttley, R Breitling. Defining informative priors for ensemble modeling in systems biology (2018) Nature Protoc 13:2643-2663

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