Genomic/Genetic Approach To Malaria Parasite Development

疟疾寄生虫发育的基因组/遗传学方法

• 批准号: 6507113
• 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/6507113
• 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; single nucleotide polymorphism

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 dynamics. 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 larger 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 also be used to study parasite population genetics and transmission dynamics in endemic areas. Another research interest of our lab is the study of gene function and gene interactions by expressional analysis using microarray and proteomic methods. We are using these techniques to study protein expression in the parasite food vacuole as well as stages of early sexual development. Various proteins from the food vacuole and stages of gametocyte development have been identified using 2-D gels and mass spectrometry. 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.

疟疾基因组股利用疟疾寄生虫基因组数据库，开发新的资源，研究抗药性机制、寄生虫性发育过程中的基因调控以及寄生虫种群多样性和动态。这方面的一个项目是用数百个微卫星标记对恶性疟原虫田间分离株进行基因分型，以确定与耐药性相关的染色体位点。一个世界范围内收集的90个寄生虫分离株已被分型与342个标记，并揭示了，除了候选位点的耐药性，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。另一个项目是收集来自寄生虫转运蛋白基因的单核苷酸多态性（SNP）以及SNP与药物反应的关联。已经鉴定了多种候选基因。我们还在为更大规模的研究开发资源，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）全球寄生虫分离株的收集; 3）。恶性疟原虫单倍体基因组关联分析的统计和计算机程序。从四个寄生虫分离株中已经测序了大约400个染色体2和3上的基因，并且已经鉴定了数百个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药和营养变化的反应。这些工具还将用于研究流行地区的寄生虫种群遗传学和传播动态。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学方法进行表达分析来研究基因功能和基因相互作用。我们正在使用这些技术来研究寄生虫食物泡中的蛋白质表达以及早期性发育阶段。已使用二维凝胶和质谱法鉴定了来自食物液泡和配子母细胞发育阶段的各种蛋白质。我们还使用来自寄生虫基因组的6300个寡核苷酸打印了微阵列载玻片，并做了一些初步的杂交实验。在鉴定候选基因后，将进行详细的生化和遗传表征。