Understanding the genetic basis of social behaviour from honey bee and other insect models

我的研究项目是社会生物学，将基因组学和亲属理论结合起来，详细阐述社会行为的遗传基础。我的研究理由很简单：50年来，亲属理论为社会性提供了一种基于基因的解释，但在大多数情况下，我们还没有确定这些基因。在过去的五年里，我利用基因组技术找出了突出一个典型的社会特征的基因：工蜂的生殖利他主义。我已经确定，编码蛋黄、蜂王浆和数十种其他蛋白质的基因可以调节繁殖自私(女王)和利他(工人)种姓之间的差异，在理论和发现之间架起了一座清晰的桥梁。此外，我已经开始将这些基因组装成相互作用网络，首次描述了不育是如何在分子水平上协调的。因此，我之前的发现基金成功地使我和我的学生们能够将我们对社会生物学的理解从基因理论推向基因现实。在接下来的五年里，我提议通过三种截然不同的方式进一步改变这一领域。*首先，我们的工人不育多基因网络引起了社会生物学和养蜂界的极大兴趣。因此，我需要对这些网络的生殖功能进行实验验证，这一过程最好是通过计算机支持的信息学来启动。我和我的学生将从网络拓扑和相关的基因组数据中确定哪些基因具有核心重要性，哪些功能最具代表性，以及关于生殖调控的分子生物学的先前想法是否得到支持。其次，我们正在开发第二个昆虫模型，与蜜蜂的这些发现相辅相成。果蝇并不是严格意义上的群居动物，但我的实验室发现，我们可以使用蜂王信息素让雌性果蝇进入类似蜜蜂的不育状态。这一非凡的发现具有激动人心的实验意义。首先，我们可以在以果蝇为基础的靶向基因表达系统中敲除蜜蜂的同源物。*最后，我的实验室一直在将我们与蜜蜂相关的研究与一种与蜜蜂无关的群居昆虫进行比较。白蚁完全是社会性的，但很少被用作发现社会性基因的工具。我的实验室正在开发东方地下白蚁，将其作为与蜜蜂相似的模型，我们可以挖掘与种姓和社会性相关的基因。我的实验室对二倍体白蚁转录组的构建和分析将首次测试白蚁的社会性是否涉及与单二倍体蜜蜂不同的基因。随着社会生物学走向对社会进化的更广泛的理解，我的三个模型研究项目也成熟了；它被很好地结合在一起，非常适合培训学生在亲缘关系理论和分子技术方面，并从事养蜂业和工业病虫害防治部门。

My research program in sociobiology couples genomics and kin theory to detail the genetic basis of social behavior. My research rationale is straightforward: for 50 years kin theory has provided a gene-based explanation for sociality, but for the most part we have yet to identify those genes. Over the past five years, I have capitalized on genomic techniques to identify genes that underscore one quintessentially social trait: reproductive altruism in worker honeybees. I have established that genes encoding egg yolk, royal jelly and dozens of other proteins can mediate differences between reproductively selfish (queen) and altruistic (worker) castes, providing a clear bridge between theory and discovery. Moreover, I have begun to assemble these genes into interaction networks that provide a first description of how sterility is coordinated at the molecular level. My previous Discovery grant has therefore successfully enabled my students and I to push our understanding of sociobiology from gene theory to gene reality. In the next five years I propose to further transform the field in three distinct ways. ******First, our multi-gene networks for worker sterility are of tremendous interest to the sociobiological and apicultural communities. I therefore need to experimentally verify these networks for reproductive function, a process that is best initiated through computer-supported informatics. My students and I will identify, from the network topologies and associated genomics data, what genes are of central importance, what functions are most represented, and what prior ideas regarding the molecular biology of reproductive regulation are supported, if any. Second, we are exploiting a second insect model that complements these findings from the bee. Drosophila is not strictly social, but my lab has discovered that we can use queen bee pheromone to `trick' female flies into a state of bee-like sterility. This remarkable discovery has exciting experimental implications. For one, we can knock-down bee homologues within a Drosophila-based targeted gene expression system. ******Finally, my lab has been juxtaposing our bee-related research against a social insect unrelated to bees. Termites are fully eusocial, yet are rarely used as a vehicle for social gene discovery. My lab is developing the Eastern subterranean termite as a model comparable to the honeybee that we can mine for genes associated with caste and sociality. My lab's construction and analysis of a diploid termite transcriptome will provide a first test of whether termite sociality involves genes different to those employed by haplo-diploid bees. As sociobiology matures towards a more general understanding of social evolution, my three-model research program has also matured; it is well integrated, is ideal for training students in kin theory and in molecular technique, and engages the apicultural and pest control sectors of industry.