Lipid engineering in cell membranes and whole organisms

Biology is organized by membranes whose lipid composition can vary tremendously across cells, tissues, organelles, and disease states. Lipids dictate the physical and chemical properties of cell membranes, yet have been traditionally difficult to manipulate and study in living systems. We harness synthetic and chemical biology approaches in a variety of systems – ranging from artificial cells to whole animal models – to control the properties and structure of lipid membranes in order to understand their functional roles in biology.

In addition to fundamental research, we are interested in harnessing knowledge of lipid and membrane biology for applications in health and technology. Many human diseases, such as type 2 diabetes and Alzheimer’s, are characterized by dysregulation of lipid homeostasis in affected cell types. Membranes also serve as the primary barrier for delivering drugs and other therapeutics to intracellular targets and new approaches to specifically breach them are sorely needed. In biotechnology, membranes are the site of chemical toxicity for microbial cell factories, so engineering lipid composition is a strategy for enhancing their performance in industrial environments.

A human cell colored by a membrane fluidity sensitive lipid-dye showing the properties of different organelle membranes. Can we program the composition of different membranes in complex cells? Can this be used to model the effects of lipid dysregulation in human diseases?
Vials of fruit flies that have been fed different lipid-defined diets and show strikingly differing activities under these conditions. Can we understand how lipids dictate tissue-specific functions, such as in the brain, in animal model systems?
Artificial membrane vesicles. Can synthetic systems be designed to better understand the design principles behind cells and their organelles? Can the synthesis and exchange of lipids between vesicles mimic the processes that underlie complex cell function?