Functions of Branched-Chain Fatty Acids in the Nematode Worm C. elegans

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Fatty acids are an important class of lipid molecules, one of the four main building-blocks for all living tissues. Our laboratory has recently identified the branched-chain fatty acid 15-methyl hexadecanoic acid, also known as C17ISO, as required for post-embryonic growth in the nematode worm C. elegans. In the absence of this molecule, which is a methlyated palmitate and probably a catabolite of leucine, worms are unable to grow after hatching, but this arrest can be suppressed by supplementation with C17ISO. C17ISO has been implicated in the coordinated sensing of nutritional and metabolic status to allow for larval growth, but the mechanism of its action is unknown. Through genetic screens we have identified several complete-suppressor strains and a partial-suppressor strain, which suggests that C17ISO may be part of a lipid-signaling or -metabolism pathway that is essential for worm development. I propose to (1) identify the genes involved with this putative signaling pathway and (2) characterize the mechanism of the already identified partial-suppressor mutant strain. PUBLIC HEALTH RELEVANCE: Lipid molecules are required for the formation of cellular membranes, for the long-term storage of energy, and as second-messenger signaling intermediates, but among the very many lipid molecules that we know exist, few are well understood. I propose to study how a fatty-acid, a type of lipid molecule, with a branched- backbone chain is able to regulate the growth of the model organism C. elegans, a worm whose study has previously yielded important insights into the basic structure and functions of living systems. It is possible that this work will increase our understanding of the general functions of lipid molecules and therefore contribute to an increased understanding of how cells and organisms function or of the origins of metabolic diseases such as diabetes mellitus and obesity.