Malaria Parasite Sexual Development, Drug Resistance, an

疟原虫性发育、耐药性、

• 批准号: 7303881
• 负责人: Xinzhuan Su
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7303881
• 关键词: Malaria; Parasite; Sexual; Development; Drug

The Malaria Genomic Unit uses the malaria parasite genome databases and develops new resources to study the mechanism of drug resistance, gene regulation during parasite sexual development, and parasite population diversity and evolution. Now we have finished collecting single nucleotide polymorphisms (SNPs) from 3539 genes on all of the 14 chromosomes of Plasmodium falciparum. We are developing a platform that will allow us to genotype large number of SNPs. All the SNP information and some DNA have been sent a company; and we are in the process of evaluating a SNP typing chip. A manuscript describing this multi-year project is being submitted. We have finished the project studying chromosomal haplotypes, population structures, and recombination rate variation and have published a paper in PLoS Biology. The project studying the origin of P. vivax parasite has been completed too. We sequenced the mitochondrial genome from 176 P. vivax isolates and 5 other primate malaria species. Our data support the hypothesis of host switches and origin of P. vivax from Asian monkeys. The results were published in Mol. Biol. Evol. Another major effort of our laboratory is to study gene expression and regulation associated with the parasite sexual differentiation. We have identified a gene that may play a key role in gametocyte development using microarray and genetic mapping. The results from this study have also been published in PNAS. We are in the process of growing parasite isolates for genotyping using the SNP typing technology we are developing and a high density Affymatrix tiling array. We hope to use these methods and field parasites to locate loci that are associated with different drug resistant and parasite development phenotypes. We are still interested in various aspects of parasite sexual development, particularly the biological functions of Pfmdv1 and other genes that may involve in the process of gametocyte development.

疟疾基因组单位使用疟疾寄生虫基因组数据库并开发新的资源，以研究抗药性的机制、寄生虫性发育过程中的基因调控以及寄生虫种群的多样性和进化。目前，我们已经完成了对恶性疟原虫全部14条染色体上3539个基因的单核苷酸多态(SNPs)的收集。我们正在开发一个平台，使我们能够对大量的SNPs进行基因分型。所有的SNP信息和一些DNA已经发送给一家公司；我们正在评估SNP打字芯片。正在提交一份描述这一多年项目的手稿。 我们已经完成了研究染色体单倍型、种群结构和重组率变异的项目，并在《公共科学图书馆·生物学》上发表了一篇论文。 间日疟原虫起源研究项目也已完成。我们对176株间日疟原虫分离株和5种其他灵长类疟疾物种的线粒体基因组进行了测序。我们的数据支持间日疟原虫的宿主开关假说和亚洲猴间日疟原虫的起源。研究结果发表在《摩尔》杂志上。比奥尔。埃沃尔。 我们实验室的另一项主要工作是研究与寄生虫性别分化相关的基因表达和调控。利用基因芯片和基因定位技术，我们已经确定了一个可能在配子体发育中起关键作用的基因。这项研究的结果也发表在PNAS上。 我们正在使用我们正在开发的SNP分型技术和高密度AffyMatrix瓷砖阵列来培养用于基因分型的寄生虫分离株。我们希望使用这些方法和野外寄生虫来定位与不同耐药和寄生虫发育表型相关的基因座。 我们仍然对寄生虫性发育的各个方面感兴趣，特别是Pfmdv1和其他可能参与配子体发育过程的基因的生物学功能。