EASTBIO: Inflammatory Fat: Understanding how the immune system drives adipose tissue dysfunction using spatial lipidomics


   School of Medicine, Medical Sciences & Nutrition

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  Prof Jules Griffin, Prof Heather Wilson  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This fully funded, 4-year PhD project is part of a competition and is funded by the BBSRC EASTBIO Doctoral Training Partnership and Stiryx Therapeutics Limited.

In obesity, adipose tissue can become inflamed with the infiltration of immune cells, particularly macrophages, which surround adipocytes to create crown-like structures. These structures have been associated with increased release of pro-inflammatory signals such as cytokines and lipid signalling molecules (lipid mediators). This process can tip the body from a healthy storage of fats to a state associated with systemic inflammation which may contribute to a number of chronic diseases including cardiovascular disease, fatty liver disease and type 2 diabetes. However, we do not understand how this process initially develops in healthy individuals.

We have been using metabolomics and lipidomics to better understand how inappropriate fat metabolism contributes to cell dysfunction [1]. This project will develop lipidomic tools to profile lipid mediators generated in adipose tissue taken from obese individuals, who are otherwise healthy to understand the early mechanistic changes that accompany adipose tissue inflammation – a process referred to as metainflammation. Specifically, we will use liquid chromatography mass spectrometry to profile lipid signalling molecules including eicosanoids, ceramides and diacylglycerols [2] in adipose tissue taken from patients undergoing bariatric surgery. Parallel to this, macrophage infiltration will be measured by microscopy and cell staining as well as the novel approach of mass spectrometry imaging allowing us to probe metabolic changes at the single cell level. We will use multivariate statistics to combine the -omic datasets to understand how macrophage infiltration is associated with the production of inflammatory lipid signalling molecules. This project is in collaboration with the biotech company Sitryx and the student will use the company’s expertise in molecular biology, metabolism and immunology to model the changes detected adipose tissue using in vitro approaches to target specific pathways in adipocytes and macrophages.

This studentship would best suit a biologist/biochemist/chemist with experience of mass spectrometry and/or immunology. However, we do not expect candidates to have all the relevant skills for this studentship and we will provide training in mass spectrometry, immunology and multivariate statistics as required.

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ELIGIBILITY:

Applicants should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject. Those with a 2:2 UK Honours degree (or international equivalent) may be considered, provided they have (or are expected to achieve) a Distinction or Commendation at master’s level.

All students must meet the eligibility criteria as outlined in the UKRI guidance on funding for postgraduate training and development. This guidance should be read in conjunction with the UKRI Training Grant Terms and Conditions.

This project is available to undertake part-time if preferred.

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APPLICATION PROCEUDRE:

  • Please visit this page for full application information: How to apply | eastbio (eastscotbiodtp.ac.uk)
  • Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at [Email Address Removed]
  • Two references should be provided by the deadline using the EASTBIO reference form. References should be sent to [Email Address Removed]
  • Unfortunately, due to workload constraints, we cannot consider incomplete applications.
  • CV's submitted directly through a FindAPhD enquiry WILL NOT be considered.
  • If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at [Email Address Removed]
Biological Sciences (4) Food Sciences (15) Mathematics (25) Medicine (26) Nursing & Health (27)

Funding Notes

This fully funded, 4-year PhD project is funded by the EASTBIO BBSRC Doctoral Training Partnership and Stiryx Therapeutics Limited.
This opportunity is open to UK and International students (The proportion of international students appointed through the EASTBIO DTP is capped at 30% by UKRI BBSRC).
EASTBIO studentships includes a UKRI doctoral stipend (estimated at £18,622 for the 2023/2024 academic year – rate not yet set for 2024/2025), plus a training grant of £5,000 per annum (year 1-3; £1,500 year 4) and a travel/conference grant of £230 per annum.
EASTBIO does not provide funding to cover visa and associated healthcare surcharges for international students.

References

1. Towards metabolic biomarkers of insulin resistance and type 2 diabetes: progress from the metabolome. Roberts LD, Koulman A, Griffin JL. Lancet Diabetes Endocrinol. 2014;2(1):65-75.
2. A Comprehensive UHPLC Ion Mobility Quadrupole Time-of-Flight Method for Profiling and Quantification of Eicosanoids, Other Oxylipins, and Fatty Acids. Hinz C, Liggi S, Mocciaro G, Jung S, Induruwa I, Pereira M, Bryant CE, Meckelmann SW, O'Donnell VB, Farndale RW, Fjeldsted J, Griffin JL. Anal Chem. 2019 Jul 2;91(13):8025-8035.

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