Extraordinary pH - the mechanism of generation of pH 12 in living systems

昆虫在与人类的互动中既是至关重要的，也是致命的。虽然世界上几乎所有的农作物都是通过昆虫授粉的，但每年有100多万人死于虫媒疾病，世界上20%的农作物死于虫害。昆虫对许多最有用的杀虫剂产生了抗药性，在过去的十年里，很少有新的杀虫剂被推向市场。更好地理解是什么让昆虫如此成功(就物种而言，它们是地球上的主导生命形式！)因此，在使我们能够找到新的、有选择的方法来消除有害害虫方面，这一点至关重要。许多最有害的昆虫(叮咬苍蝇和蚊子传播疾病，以及破坏农作物的毛虫)都有生物学上独一无二的特性；它们的部分肠道在异常碱性的pH下运行，高达12。如果我们能找出这种高pH值是如何产生的，我们就有了一个独特的、选择性的目标，让我们能够有选择地攻击有害昆虫。我们的策略是确定在疟疾和黄热病蚊子以及家蚕毛虫肠道的高pH值区域高水平表达的基因。然后，这些基因将直接在这些物种中被敲除，或者在果蝇(果蝇)中被敲除，果蝇是一种相关昆虫，遗传工具对其特别强大。如果通过这种干预降低肠道pH值，那么我们将识别出开发新杀虫剂的潜在靶标基因。

Insects are both vital and deadly in their interactions with humans. Although nearly all the world's crops are pollinated by insects, over a million people a year die from insect-borne diseases, and 20% of the world's crops are lost to insect attack. Insects are becoming resistant to many of our most useful insecticides, and few new ones have been brought to market in the last decade. An improved understanding of what makes insects so successful (in terms of species, they are the dominant life form on earth!) is thus vital in allowing us to find new, selective ways of eliminating harmful pests. Many of the most harmful insects (biting flies and mosquito vectors of disease, and crop-destroying caterpillars) have a specialization that is unique in biology; they run part of their guts at extraordinarily alkaline pH, as high as 12. If we can find out how this high pH is generated, we have a unique, selective target that allows us to attack harmful insects selectively. Our strategy is to identify genes that are expressed at high levels in the high-pH regions of the guts of the malaria and yellow fever mosquitoes, and the Bombyx silkworm caterpillar. Such genes will then be knocked out, either in these species directly, or in Drosophila (the fruit fly), a related insect for which genetic tools are particularly powerful. If gut pH is knocked down by such intervention, then we will have identified potential target genes for the development of new insecticides.