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

描述（由申请人提供）：脂肪酸是一类重要的脂质分子，是所有活组织的四个主要组成部分之一。我们的实验室最近发现了支链脂肪酸15-甲基六酸，也被称为C17ISO，是线虫胚胎后生长所需要的。这种分子是一种甲基化棕榈酸酯，可能是亮氨酸的分解代谢物，在缺乏这种分子的情况下，蠕虫在孵化后无法生长，但这种停滞可以通过补充C17ISO来抑制。C17ISO被认为与营养和代谢状态的协调感知有关，以使幼虫生长，但其作用机制尚不清楚。通过基因筛选，我们已经鉴定出几个完全抑制菌株和一个部分抑制菌株，这表明C17ISO可能是蠕虫发育所必需的脂质信号或代谢途径的一部分。我建议(1)确定与这个假定的信号通路有关的基因，(2)描述已经确定的部分抑制突变株的机制。

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.