Understanding the molecular mechanism of bacterial sphingolipid synthesis

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Bacteria produce a wide range of membrane lipids and our understanding of these is growing, with recent work showing that they produce lipids that were previously thought to only be produced by eukaryotes, including an array of different sphingolipids. Sphingolipids are key structural components of eukaryotic membranes, and they also play key roles in intra- and inter-cellular signalling. Recently they have been discovered in key human microbiome species, including Bacteroides thetaiotaomicron and Escherichia coli.The project aims are to determine the structure and function of the key enzymes involved in the early stages of sphingolipid biosynthesis in E. coli and understand how the expression of these enzymes is regulated in response to environmental and host factors. In this project the student will use molecular cloning to produce protein expression constructs; they will produce recombinant protein in an Escherichia coli expression host; and use chromatography methods to purify the recombinant proteins. The student will develop skills in structural biology and biochemistry methods to characterise the structure and function of these proteins. This multidisciplinary project combines expertise in structural biology and biochemistry with expertise in the study of gene regulatory networks in key host/microbe interactions additional expertise in structural biology will come from Durham partner. The student will also have extensive opportunities to work with our collaborators at Edinburgh University and Rutgers University. Ultimately this project will help us develop our understanding of the biosynthetic pathways used by bacteria to produce these important membrane lipids and how their expression is controlled in a host context. The project outcomes will have impact in understanding host microbe interactions and may provide new targets for the development of antimicrobial molecules.