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The University of Southampton

Research project: Attard: Data-driven approaches to the systems biology of lipid biosynthesis

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The aim of this research programme is to use data from quantitative lipidomic studies to determine the extent to which membrane curvature elastic energy accounts for lipid homeostasis in both eukaryotic and prokaryotic cells.key words: lipid membrane, lipidomics, systems biology, biochemical pathways, curvature elastic energy, data-driven modelling.

Research in this area is concerned with the question of how cells control the complex lipid compositions that characterise their cell membranes. When considering that the membranes in a typical eukaryotic cell may contain 400-800 different types of lipids, with the different types differing in number densities by orders of magnitude, it is not surprising that cells do not control the composition of each lipid species. Instead it appears that cells regulate broad classes of lipids. Previous work has suggested that the lipid composition of membranes may be controlled to maintain the membrane curvature elastic energy within certain bounds, and that the precise chemical nature of the lipid species used is not important. We have conducted extensive lipidomic studies of eukaryotic cells in culture and using a data-driven modelling approach we have found that the data are consistent with regulationof lipid composition being driven by control function that depends on the ratio of two lipid classes. Current projects build on these observations. We are extending our lipidomic data sets to prokaryotes (E. coli, B. subtilis and Shewanella oneidensis) as well as single celled eukaryotes (Thalassosira pseudonana). In these studies we use mass spectrometry to quantify the lipid compositions for well-defined cell populations exposed to a range of perturbations (e.g. nutirients, salinity, pH). In the case of eukaryotic organisms we are also using subcellular fractionation to map the lipidomes of cellular organelles. The overall aim is to apply the data-driven approaches we have developed to these new data sets and infer the control architectures of their lipid biosynthetic networks. These projects are in collaboration with Anthony Postle and Alan Hunt (Medicine), Rachel Mills (Ocean & Earth Science), Marcus Dymond (Pharmacy & Biomolecular Sciences, University of Brighton), Richard Templer and Oscar Ces (Chemistry, Imperial College, London).

Related research groups

Chemical Biology, Diagnostics and Therapeutics
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