Karl Lohmann PhD Prize

Johannes Morstein

Development and Application of Photoswitchable Lipids

Photoswitchable lipids are emerging tools for the precise manipulation and study of lipid function. Optical control of lipid structure is attained through the incorporation of a hydrophobic molecular photoswitch (azobenzene) into the fatty acid tails of lipids. I demonstrate that this approach is broadly applicable to glycerolipids, sphingolipids, and other natural and synthetic amphiphilic pharmacophores. These include the sphingolipids ceramide, sphingosine, and sphingosine-1-phospate, the glycerolipids phosphatidic acid, lysophosphatidic acid, and phosphatidylcholine, and multiple nuclear hormone receptor ligands. The applications of these tools include modulation of membrane biophysics, including permeability, fluidity, lipid mobility and domain formation. Photoswitchable lipids are also very useful in lipid physiology and enable optical control of a wide array of lipid receptors, such as ion channels, G protein-coupled receptors, nuclear hormone receptors, and enzymes that translocate to membranes. Enzymes involved in lipid metabolism often process them in a light-dependent fashion. The utility of photoswitchable lipids for the optical control of physiology was demonstrated in a large range of different applications from biochemical and cellular systems to animal models. For example, our photoswitchable analog of sphingosine-1-phosphate has been tested in both cellular assays, and in vivo behavioral assays and was then used by other research groups for the discovery of new signaling function in brain slice models. Photoswitchable lipids are versatile tools that enable optical control of lipid metabolism and function, and meet a critical need to illuminate lipid biology.