The clag gene family of P. falciparum; examining roles in cytoadherence, rheological properties or tissue trophism.

恶性疟原虫的 clag 基因家族；

• 批准号: nhmrc : 199608
• 负责人: A/Pr Donald Gardiner
• 金额: $ 30.14万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/clag-gene-family-tissue-trophism/96438
• 关键词: clag; gene; family; P.; falciparum

There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene. Most Australians know of clag as a glue, and our data provides evidence that it sticks the parasitised red cells to veins via a protein called CD36 on the internal surface of veins. Our evidence for this has been published in two prestigious international journals. We propose here to examine the same gene in a mouse malaria model as it should be highly informative to see what effect destoying clag has on the disease in a living animal. Obviously this cannot be tested in people. It has now become clear that there are a number of slightly different clag genes and we do not know what the others do. We propose here that they may enable the parasitised red cells to stick to targets other than CD36 on the surfaces of veins, or affect blood flow of infected cells, or direct the parasitised red cells to other organs. The experiments that we propose should reveal whether these ideas are true.

全世界每年约有5亿疟疾病例，每年约有200万人死亡。包括脑型疟疾在内的严重疟疾是死亡的主要原因。它是由含有疟疾寄生虫的红细胞粘在微小静脉的内层并堵塞它们引起的；之后会发生什么是复杂的。黏附的过程称为细胞黏附。我们发现了一种在这种粘着过程中起重要作用的基因。我们用首字母缩写CLAG来称呼它，意为细胞黏附连接的无性基因。大多数澳大利亚人知道CLAG是一种粘合剂，我们的数据提供了证据，证明它通过静脉内表面一种名为CD36的蛋白质将寄生的红细胞粘在静脉上。我们的证据已经发表在两个享有盛誉的国际期刊上。我们建议在小鼠疟疾模型中检查相同的基因，因为它应该是非常有用的，以了解去除CLAG对活动物的疾病有什么影响。显然，这不能在人体上进行测试。现在已经很清楚，有一些略有不同的CLAG基因，我们不知道其他的基因是做什么的。我们在这里提出，它们可能使寄生的红细胞附着在静脉表面CD36以外的靶点上，或影响感染细胞的血流，或将寄生的红细胞引导到其他器官。我们提出的实验应该会揭示这些想法是否属实。