Functional genomics of the insect epitheliome

昆虫（就物种而言）是地球上最多样化的生物群体，它们在体型和生活方式上都表现出惊人的多样性。昆虫的大小从不足一毫克到80克不等；它们可以在陆地、淡水和咸水湖、从赤道到南极生存。值得注意的是，所有这些多样性都被相同的身体计划所容纳。它们成功的关键是它们在面对饮食和环境挑战时严格调节内部环境的能力。这种控制大部分是通过上皮进行的；排列在消化道上的特化细胞片。在最近的工作中，我们确定了四种关键昆虫上皮细胞共有的核心基因指纹（“上皮组”）；唾液腺、中肠、马尔比氏（肾）小管和后肠。尽管它们发挥着不同的作用（分别是唾液分泌、消化吸收、排泄和选择性重吸收），但它们都依赖于一组共同的分子泵、通道和转运体。该项目的目的是测试该基因表达模型的有效性，使用在果蝇中唯一可用的遗传和转基因工具的组合，选择性地破坏其他正常昆虫中单个上皮中单个基因的功能。这些基因敲除或过表达方案的影响将通过一系列生理试验进行评估，其中许多是我们小组开发的。被靶向的基因群包括关键转运蛋白，被认为调节转运并产生最佳功能的细胞信号基因，以及控制基因表达并赋予每个上皮细胞独特特性的关键转录因子。该项目将开创一个比较上皮组学的新学科，并将产生有价值的见解和持久的资源，可以在未来用于解决整个昆虫多样性，包括关键的有益生物（如蜜蜂），以及农业、兽医和医疗害虫。

Insects are (in terms of species) the most diverse group of organisms on earth, and show astonishing variability, both in size and lifestyle. Insects can range in size from well under a milligram, right up to 80g; they can survive on land, freshwater and saline lakes, and from the equator to the Antarctic. Remarkably, all of this diversity is accommodated by the same body plan. Critical to their success is their ability to tightly regulate their internal milieu in the face of dietary and environmental challenges. Most of this control is through their epithelia; sheets of specialized cells that line their alimentary canal. In recent work, we identified a core fingerprint of genes (the 'epitheliome') that is common to the four critical insect epithelia; the salivary glands, midgut, Malpighian (renal) tubules and the hindgut. Although they perform different roles (secretion of saliva, digestion and absorption, excretion and selective reabsorption, respectively), all show a reliance on a common set of molecular pumps, channels and transporters.The aim of this project is to test the validity of this gene expression model, using a combination of genetic and transgenic tools uniquely available in the fruit fly Drosophila melanogaster, to selectively disrupt the function of individual genes in individual epithelia within an otherwise normal insect. The impact of these knockdowns or overexpression protocols will be assessed with a battery of physiological assays, many developed by our group. Gene groups to be targeted include key transporters, cell signaling genes that are thought to regulate transport and so produce optimal function, and the key transcription factors that control gene expression and give each epithelium its unique properties. This project will pioneer a new discipline of comparative epitheliomics, and will produce valuable insights and lasting resources that can be employed in the future to address the whole of insect diversity , including key beneficials (such as bees), and agricultural, veterinary and medical pests.