Unravelling the function of the Nha gene family

点击翻译按钮获取中文摘要

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.