Unravelling the function of the Nha gene family

大约三分之一的人类基因组（实际上是任何生物体基因组的三分之一）是用于调节跨膜运输的基因。运输对生存至关重要，有缺陷的运输基因引起的遗传疾病就证明了这一点；囊性纤维化在凯尔特国家尤为突出。考虑到运输的重要性，令人惊讶的是，有多少基因仍然需要实验赋予它们的功能。最近，一类新的交换基因CPA2被发现。它可以从细菌到人体中被发现，并将钠离子交换为氢离子。两种人类基因中的一种已经被确定为原发性高血压和骨吸收的候选基因——这两个过程对人类衰老至关重要。因此，找出CPA2基因家族在高等生物中的作用是很重要的。我们计划在一个已建立的遗传模型中研究CPA2基因，果蝇黑腹果蝇（Drosophila melanogaster）（和人类一样）有两个CPA2家族成员。使用果蝇有几个优势：工作更快（只需要三个月就能培育出一只转基因果蝇），更便宜（只需要几十英镑就能让一群果蝇存活一年），而且道德（不需要在哺乳动物身上做实验）。因此，我们认为在果蝇身上的工作是对人类医学研究的一个令人兴奋的补充，也是其他实验室可能产生的小鼠模型的补充。我们的工作将集中在确定这些基因的作用，特别是在果蝇的“肾脏”中，我们最近发现这些基因在那里被强烈表达。我们将在试管中研究蛋白质的运输特性，并利用这些信息来解释它们对整个生物体的功能有何贡献。昆虫本身就很重要，因为每年有一百多万人死于疟疾；世界卫生组织声称，世界上三分之一的作物在田间或储存中因昆虫袭击而损失。我们计划将我们的结果扩展到果蝇的近亲——蚊子，以看看我们的结果是否适用于所有昆虫。如果是这样，CPA2家族可能成为新型杀虫剂的靶点。

Around a third of our genome (indeed, a third of any organism's genome) is devoted to genes that mediate transport across membranes. Transport is essential to survival, as evidenced by genetic diseases caused by defective transport genes; cystic fibrosis is a particularly prominent example in Celtic countries. Given the importance of transport, it is surprising how many genes still need function ascribed to them experimentally. Recently, a new class of exchanger gene called CPA2 has been identified. It can be found from bacteria to humans, and exchanges sodium ions for hydrogen ions. One of the two human genes has already been identified as a candidate in essential hypertension, and in bone resorption - two processes central to human ageing. It is thus important to find out what the CPA2 gene family does in higher organisms. We plan to study the CPA2 genes in an established genetic model, the fruit fly Drosophila melanogaster where (as in humans) there are two CPA2 family members. Using Drosophila confers several advantages: the work is quicker (it takes only three months to generate a transgenic fly), cheaper ( it takes only tens of pounds to keep a line of flies alive for a year), and ethical (no experiments on mammals are required). We thus see work in Drosophila as an exciting adjunct to continuing medical study of humans, and the likely generation of mouse models in other labs. Our work will focus on identifying what the genes do, particularly in the fly 'kidney' where we have recently shown that the genes are strongly expressed. We will study the transport properties of the protein in the test tube, and use the information to explain what they may contribute to the functioning of the whole organism. Insects are important in their own right, as over a million lives are lost to malaria alone each year; and the WHO claim that a third of world crops are lost to insect attack in the field or in storage. We plan to extend our results to close relatives of Drosophila, the mosquitoes, in order to see whether the results we have generated are applicable across the insects. If so, the CPA2 family may be targets for novel insecticides.