Metabolomic analysis and membrane transport proteins in the malaria parasite

疟疾寄生虫的代谢组学分析和膜转运蛋白

• 批准号: nhmrc : 316933
• 负责人: Prof Kiaran Kirk
• 金额: $ 24.6万
• 依托单位: Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/metabolomic-analysis-membrane-malaria-parasite/78076
• 关键词: Metabolomic; analysis; membrane; transport; proteins

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.

疟疾寄生虫是一种单细胞有机体，它会入侵感染者的红细胞。目前还没有疫苗，这种寄生虫对我们现有的药物正变得越来越耐药。因此，迫切需要新的抗疟疾战略。这一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的大多数基因起什么作用，这并不是一件简单的事情。阻碍我们努力开发新的抗疟疾药物的因素之一是，我们对寄生虫赖以维持其在红细胞内高生长和复制的各种生化途径以及使其产生抗药性的生化机制的了解相对较差。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。我们将研究这种变化如何应对营养匮乏，应对在抗疟疾耐药性中发挥关键作用的基因突变，以及应对编码蛋白质的基因表达的变化，我们认为这些蛋白质参与了寄生虫吸收营养的过程。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，它将为正在运行的以及可能成为新药靶点的生化途径提供新的见解。这项工作可能会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，该策略可能非常有用，有助于我们将功能归因于参与这种重要人类病原体生物化学的许多基因。