SGER: Manipulation of gene expression in honey bees with RNAi

随着人类基因组计划催生的技术的出现，行为科学正准备取得革命性的进步。然而，目前阻碍行为学界接受基因组学的一个问题是，操纵基因表达的技术仅适用于少数物种。双链RNA是一种非常有效的干扰秀丽隐杆线虫和黑腹线虫基因表达的技术。与反义寡核苷酸治疗相比，“RNAi”的作用具有高度的特异性和更强的一致性。罗宾逊博士试图将RNAi的应用扩展到蜜蜂，这是一种缺乏生殖系转化技术的社会生物学模式生物。罗宾逊博士将测试这样一个假设，即来自周期（每个）基因的dsRNA抑制每个mRNA并导致两个行为过程的变化：实验室中的运动行为昼夜节律，以及劳动分工，即从蜂房工作到野外觅食的转变。蜜蜂的per系统是一个理想的测试案例，这与我实验室中可用的分子和行为分析以及从果蝇观察到的per不是致命基因有关。由于两个科学原因，测试RNAi对蜜蜂系统的影响也是令人信服的。首先，它将深入了解蜜蜂大脑中与劳动分工相关的per mRNA水平的惊人和以前无法想象的变化。其次，它将有力地展示RNAi技术的多功能性。如果RNAi不能抑制蜜蜂的per mRNA，这一结果也将具有很高的影响，因为它将在文献中提供第一个警告，即RNAi可能不是我们所希望的万灵药。

With the advent of technologies spawned by the Human Genome Project, the behavioral sciences are poised to make revolutionary advances. However, one problem that currently prevents the behavioral community from embracing genomics is that techniques of manipulating gene expression are only possible for a few species. Treatment with double-stranded (ds) RNA is providing to be a very effective techinique for interfering with gene expression in C. elegans and D. melanogaster. The 'RNAi' effect is highly specific and is strongerand more consistent than treatment with antisense oligonucelotides. Dr. Robinson seeks to extend the use of RNAi to the honey bee, a model organism in sociobiology that lacks technology for germ-line transformation. Dr. Robinson will test the hypothese that dsRNA from the period (per) gene suppreses per mRNA and causes changes in two behavioral processes: locomotor behavior circadiean rhythms in the laboratory, and division of labor, i.e., the transition from working in the hive to foraging, in the field. The bee per system is an ideal test case for progmatic reasons related to the molecular and behavioral assays available in my laboratory and the observation from Drosophila that per is not a lethal gene. Testing the effect of RNAi on the bee per system also is compelling for two scientific reasons. First, it will provide insight into the striking and previously unimagined changes in per mRNA levels in the bee brain that occur in association with division of labor. Second, it will provide a powerful demonstration of the versatiality of the RNAi technique. If RNAi does not suppress per mRNA in bees, this result also will be of high impact, because it will provide the first cautionary note in the literature that RNAi may not be the panacea that we all hope it will be.