Malaria Parasite Sexual Development, Drug Resistance, an

疟原虫性发育、耐药性、

• 批准号: 6669897
• 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/6669897
• 关键词: Plasmodium falciparum; developmental genetics; drug resistance; genetic markers; genetic polymorphism; genome; malaria; microarray technology; microorganism culture; microorganism growth; molecular biology information system; pharmacogenetics; proteomics; protozoal genetics

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. One project in this direction is the genotyping of Plasmodium falciparum field isolates with hundreds of microsatellite markers to identify chromosome loci associated with drug resistance. A worldwide collection of 90 parasite isolates have been typed with 342 markers and have revealed, in addition to candidate loci for drug resistance, important information on parasite genome structure, diversity, drug selective sweeps, and evolutionary relationships. Another project is the collection of single nucleotide polymorphisms (SNP) from the parasite transporter genes and the association of the SNP to drug responses. Various candidate genes have been identified. We are also developing resources for large scale studies to include: 1) A genome-wide SNP database with at least one SNP per gene, integrated with MS markers; 2) A worldwide collection of parasite isolates; 3). Statistical and computer programs for association analysis specific for the haploid genome of P. falciparum. About 400 genes on chromoosme 2 and 3 have been sequenced from four parasite isolates and hundreds of SNP have been identified. With these resources, we can concentrate on phenotype evaluation and measurement, including parasite responses to various antimalarials and nutrient changes. These tools will be used to study parasite population genetics and transmission dynamics in endemic areas. We are also studing polymorphisms in the mitochndria genome to infer the parasite population history, including migration and population expansion. Another research interest of our lab is the study of gene function and gene interactions by expressional analysis using microarray and proteomic methods. We have also printed microarray slides using 6300 oligonucleotides derived from the parasite genome and have done some preliminary hybridization experiments. Detailed biochemical and genetic characterization will follow after identification of candidate genes.

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。这个方向的一个项目是利用数百个微卫星标记对恶性疟原虫野外分离株进行基因分型，以确定与耐药性相关的染色体基因座。全世界范围内的90个寄生虫分离株已经用342个标记进行了分型，除了候选的抗药性基因座外，还揭示了关于寄生虫基因组结构、多样性、药物选择性扫描和进化关系的重要信息。另一个项目是收集寄生虫转运蛋白基因的单核苷酸多态(SNP)，并将其与药物反应联系起来。各种候选基因已经被识别出来。我们还在为大规模研究开发资源，包括：1)全基因组SNP数据库，每个基因至少有一个SNP，与MS标记整合；2)世界各地的寄生虫分离株集合；3)。针对恶性疟原虫单倍体基因组进行关联分析的统计和计算机程序。已从4个寄生虫分离株中对染色体2和3上的约400个基因进行了测序，并鉴定了数百个SNP。有了这些资源，我们可以集中精力进行表型评估和测量，包括寄生虫对各种抗疟疾药物的反应和营养变化。这些工具将用于研究流行地区的寄生虫种群遗传学和传播动力学。我们还在研究线粒体基因组的多态，以推断寄生虫的种群历史，包括迁徙和种群扩张。我们实验室的另一个研究兴趣是通过使用微阵列和蛋白质组方法进行表达分析来研究基因功能和基因相互作用。我们还用来自寄生虫基因组的6300个寡核苷酸打印了微阵列幻灯片，并进行了一些初步的杂交实验。在确定候选基因后，随后将进行详细的生化和遗传特征描述。