New frontiers in lipid research

Biology is organized by membranes whose composition can vary tremendously across cells, tissues, organelles, and disease states. These differences are encoded by changes to their lipid building blocks – often just the rearrangement of a few atoms. Cells synthesize hundreds or thousands of lipids and maintain the distinct composition of multiple membrane-bound compartments. What is the functional basis for this diversity? Through what mechanisms is it generated and maintained? How did it evolve?

Our research is based on biophysical approaches for understanding how lipids dictate the physical and chemical properties of cell membranes. Lipids have been traditionally difficult to manipulate and study in living systems, so we harness synthetic and chemical biology approaches in a variety of systems to investigate membrane composition and properties. We also use comparative systems to inform new models for the evolution of lipid chemistry and associated machinery.

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 observe the composition of different membranes in complex cells? Can this be programmed 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. How does lipid metabolism and foraging behaviors adapt to changing environments?
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?

Funding

Research in our lab is supported by extramural grants from the National Institute of General Medical Sciences (R35-GM142960), the National Science Foundation (MCB-2046303, MCB-2121854), the Department of Energy (DE-SC0022954), the Office of Naval Research (N00014-23-1-2543), the American Foundation for Aging Research/Hevolution, and the Paul G. Allen Family Foundation.