果蝇Methuselah（Mth）受体属于G蛋白偶联受体（GPCRs）家族成员，参与调节寿命、应激反应和生殖能力。在非果蝇昆虫中鉴定存在Methuselah-like（Mthl）受体基因，但对这些Mthl基因功能了解甚少。为此，我们克隆获得了2条舞毒蛾Mthl受体全长基因。前期研究发现其影响舞毒蛾生长发育，能调控下游P450基因表达，表明Mthl可能参与舞毒蛾生理功能调控。本项目拟从以下几个方面进一步探讨舞毒蛾Mthl受体基因功能：（1）鉴定Mthl受体激动剂基因；（2）Mthl受体及其激动剂对舞毒蛾寿命、生殖和抗逆性（高温、饥饿、氧化胁迫）影响；（3）Mthl受体G蛋白偶联信号转导通路分析。本项目将阐明舞毒蛾Mthl受体生理功能和信号转导通路，为揭示生物衰老机制提供新的途径，也为将来通过高通量筛选寻找选择性的Mthl受体激动剂和拮抗剂，并通过“反向药理学”的方法创制新的杀虫剂奠定基础。

Mthuselah (Mth), a G protein-coupled receptor, was originally identified in Drosophila melanogaster. Mthuselah is associated with lifespan, stress resistance and reproduction in Drosophila melanogaster. In nondrosophiline insects Mth is not present, and a number of Mthuselah-like genes (Mthl) have been identified. However, it is little known about physiological functions of these Mthl genes. Therefore, we had cloned two Mthl genes of gypsy moth. Previous studies showed effects of Mthls on growth and development of gypsy moth and regulation of down-stream P450 gene expression. These results indicated Mthl genes may be associated with regulation of physiological functions in gypsy moth. In present study, we will conduct the following projects to further explore functions of Mthl genes in gypsy moth including (1) identifying Mthl agonist genes; (2) study the effects of Mthl and its agonists on gypsy moth lifespan, reproduction and stress resistance (such as high temperature, starvation, oxidative stress); (3) characterization of G protein-coupled signal transduction of Mthl receptors in gypsy moth. These results will demonstrate physiological functions and signal transduction of Mthl genes in gypsy moth. And it will provide new pathway for understanding organism’s lifespan and formulate new pesticide by “reverse pharmacology” method based on finding selective agonist and antagonist of Mthl using high-throughout screening.