Summary
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 such as cardiovascular disease, fatty liver disease, and type 2 diabetes. However, we do not understand how this process initially develops in healthy individuals. If we can target this pathway with diet or drug interventions, we could help people live longer and healthier lives.
We have been using a combination of metabolomics and lipidomics to better understand how inappropriate fat metabolism contributes to cell dysfunction. 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 in adipose tissue taken from patients undergoing bariatric surgery. Parallel to this, macrophage infiltration will be measured by microscopy and cell staining, and we will use multivariate statistics to combine the two datasets to understand how macrophage infiltration is associated with the production of inflammatory lipid signalling molecules. This project is in collaboration with the biotechnology company Sitryx, and the student will use their expertise in molecular biology, metabolism, and immunology to model the changes detected in adipose tissue using in vitro approaches to target specific pathways in adipocytes and macrophages and better define the underlying metabolic pathways that drive metainflammation. The student will spend part of the PhD at Sitryx, gaining valuable experience in biotechnology in a commercial setting.
Qualifications
This studentship would best suit a biologist, biochemist, or chemist with experience in 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.
#J-18808-Ljbffr