Although lipids are essential contributors to numerous cellular functions, they are understudied relative to other biological molecules like proteins. While lipids have been connected to many diseases, their therapeutic potential has not yet been realised, in part due to our poor understanding of their metabolism and functions. Lipids are fundamentally small molecules and as such chemical biology approaches are essential to investigate their roles. A primary interest of my laboratory is to understand the cell biology of lipids. We are investigating the roles of lipids in a range of biological processes, including cell division, cell-cell interactions and organelle structure, using lipidomics, imaging, cell biology and chemical biology.

The endoplasmic reticulum (ER) is an important membranous organelle. Flat sheet-like cisternae and dynamic tubules define the complex network of the ER. While sheets are involved in synthesis, folding and secretion of proteins, tubules are recognised as the main sites of calcium storage, lipid synthesis, and ER’s contact with other organelles. We show here that the cellular lipid composition is crucial to maintain correct ER morphology and function. We conducted an siRNA screen in which HeLa cells were treated with 260 siRNAs targeting lipid biosynthetic enzymes. Removal of several of these enzymes, and the lipids they produce, results in dramatic changes to the ER. We have identified which lipids are changed in cells with morphological alterations and have analysed the impact of these lipidomic changes in functional assays.