Metabolomic analysis and membrane transport proteins in the malaria parasite

疟疾寄生虫是一种单细胞生物，它会侵入被它感染的人的红细胞。目前还没有疫苗，而且这种寄生虫对我们现有的药物越来越有抵抗力。因此，迫切需要制定新的抗疟疾战略。该领域的研究得到了寄生虫基因组测序的帮助。然而，我们仍然不知道寄生虫中大多数基因的作用，这不是一件直截了当的事情。阻碍我们开发新型抗疟疾药物的一个因素是，我们对疟原虫在红细胞内高速生长和复制所依赖的生化途径以及使其产生耐药性的生化机制的理解相对较差。在这项研究中，我们将使用一系列现代分析技术对寄生虫的生化成分-所谓的代谢组-进行首次详细调查。我们将研究在营养剥夺、在抗疟药物耐药性中起关键作用的基因突变以及我们认为与寄生虫摄取营养有关的编码蛋白质的基因表达变化时，这种变化是如何发生的。这个项目将为我们提供大量关于寄生虫生化组成的新信息，它将为正在运作的生化途径提供新的见解，这些途径可能成为新药的目标。这项工作可能为抗疟疾药物耐药性的机制提供新的见解。它还将形成一种策略的基础，这种策略可能非常有用，有助于我们将这种重要的人类病原体的生物化学过程中涉及的许多基因的功能归因于这种策略。

The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the things hampering us in our efforts to develop new antimalarial drugs is our relatively poor understanding of the sorts of biochemical pathways that the parasite relies on to support its high rate of growth and replication inside the red blood cell, as well the biochemical mechanisms that enable it to becomes drug-resistant. In this study we will use a range of modern analytical techniques to carry out the first detailed survey of the biochemical composition - the so-called metabolome - of the parasite. We will investigate how this changes in response to nutrient deprivation, in response to mutations in genes which play a key role in antimalarial drug resistance and in response to changes in the expression of genes encoding proteins which we believe to be involved in the uptake of nutrients by the parasite. This project will provide us with a wealth of new information about the biochemical make-up of the parasite, and it will provide new insights into the biochemical pathways that are operating and which might be targeted with new drugs. The work is likely to provide new insights into mechanisms of antimalarial drug resistance. It will also form the basis for a strategy that is likely to be extremely useful in helping us to ascribe function to the many genes involved in the biochemistry of this important human pathogen.