Molecular genetics of signaling lipids

PROJECT SUMMARY/ABSTRACT Signaling lipids, such as steroids, terpenoids, and eicosanoids, regulate diverse physiological processes in animals, including development, reproduction, and immune responses. Understanding modes of action of such lipid-derived signaling molecules, therefore, is critical for ensuring and promoting healthy development and well-being in humans. However, in contrast to proteinaceous signaling molecules such as peptide hormones and cytokines, the power of modern molecular genetics has not been fully utilized for signaling lipid research, as they are not directly encoded by genes. In the past several years, it has been demonstrated that the insect steroid hormone ecdysone requires membrane transporters for its entry into target cells, challenging the prevailing dogma in endocrinology that lipophilic hormones can simply diffuse across the plasma membrane. As exemplified by this study, there are huge knowledge gaps regarding how signaling lipids function in vivo, particularly concerning their transmembrane transport machineries. This project will utilize fruit fly genetics to reveal uncharacterized aspects of signaling pathways mediated by lipid-derived molecules. The project will focus on three major signaling lipids in insects, namely ecdysone, juvenile hormone, and eicosanoids, to better understand their modes of action. Successful completion of this project is expected not just to broaden our understanding of the functions of signaling lipids in this important model insect species, but also to provide an unprecedented example of a novel type of signaling lipid research and may inspire many researchers in the relevant field.