Generating novel photoaffinity probes to visualize lipid transport at membrane contact sites, Organic Chemistry/Cell Biology - MSc by research (Funded) Ref: 4150

The aim of this project is to develop novel probes to study the compartmentalisation and transport of specific lipids in human cells. Defects in lipid metabolism lead to a wide a range of metabolic diseases and also contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer’s. A better understanding of how lipid metabolism is orchestrated inside cells will lead to further insight into these diseases which will ultimately aid the development of new therapeutic strategies.

Lipid metabolism occurs across multiple organelles inside cells and requires lipids to be transported from one organelle to another. Lipid exchange is believed to occur at membrane contact sites but this has been difficult to measure directly, partly due to a lack of methods and tools to allow reliable visualisation and analysis of lipids in living cells. This project will use organic chemistry to develop and synthesise novel fluorescent photoaffinity probes to study cellular lipids whose faulty metabolism is linked to disease but whose cellular lifecycle remains unclear. Specifically, the project will focus on synthesis of diazirine-tagged analogues of natural lipids, which will then be tested both in vitro and in mammalian cells with the overall aim of assessing how lipids are trafficked between organelles and how this can be disrupted in disease.

The supervisory team have expertise in organic chemistry (Perry) and organelle biology (Costello) and full training would be provided in both these areas but students would ideally already have some experience and interest in chemical synthesis.