MRC PhD Studentship (University of Cambridge) Lipidomic Analysis of Endoplasmic Reticulum-stress in Obesity



Applications are invited for a MRC funded PhD studentship, to commence in October 2014, in the Lipid Profiling and Signalling (LPS) Research Group. The aim of the LPS group within MRC-Human Nutrition Research (MRC-HNR) is to understand the regulation of lipid metabolism and its interplay with health and metabolic diseases such as obesity and type 2 diabetes mellitus (T2DM).

Obesity is the strongest predictor of insulin resistance and subsequent T2DM in humans. Numerous studies of both animal models and human populations have correlated diets containing high proportions of saturated fats with increased risk of T2DM. However, while the mechanistic consequences of high blood glucose concentrations are relatively well defined in terms of the development of pathology (glycosylation of proteins, production of advanced glycation end-products, osmotic stress, etc.) the consequences of increased exposure to free fatty acids is poorly characterised.

The Endoplasmic Reticulum (ER) is a sub-cellular organelle with a key role in the synthesis and processing of proteins. Exposure of cells to high extracellular concentrations of fatty acids causes the accumulation of unfolded proteins in the ER, known as ER-stress. Prolonged ER-stress results in cell death by apoptosis.

This PhD project will use a novel lipidomic approach, developed within LPS, to better understand the consequences of ER-stress in obesity. The PhD will provide training in bioanalytical chemistry and mass spectrometry in cutting edge omic science. A successful candidate will use the Localisation of Organelle Proteomics by Isotope Tagging (LOPIT) approach to isolate the ER from adipocyte and hepatocyte cell culture models of ER-stress, and white adipose tissue and liver from animal models of obesity. The PhD candidate will then carry out lipidomic analysis of the ER from these respective models in the £2 million lipidomic mass spectrometry facility at the MRC-HNR. The ultimate aim of this project will then be to use the LOPIT-lipidomic approach to investigate the role of ER-stress in humans and its potential role in insulin resistance in collaboration with the Lipid Clinic at Addenbrooke’s hospital.

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The successful candidate will be registered with the University of Cambridge and should have or expect to obtain a BSc (Hons, 2.i or above) in Biochemistry or related life science discipline. The project will suit a student with a strong interest in T2DM and lipid metabolism. Experience of cell culture, small molecule chromatography and mass spectrometry is highly desirable. The studentship is available to UK residents and EU nationals who have been resident in the UK for at least the previous three years. Information about residence eligibility can be found at http://www.mrc.ac.uk/Fundingopportunities/Applicanthandbook/Studentships/Eligibility/index.htm

Further information about MRC-HNR can be found on our website www.mrc-hnr.cam.ac.uk). Informal enquiries should be made to Dr Lee Roberts ([email protected]).

Applicants should provide a full CV and covering letter explaining their interest in the studentship, and details of two academic referees. Please email to [email protected] via the Apply button, or post to Postgraduate Administrator, MRC-Human Nutrition Research, 120 Fulbourn Road, Cambridge. CB1 9NL.

Closing date: 6th January 2014

Anticipated Interviews: Week commencing 17th February 2014

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