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.

疟疾基因组单元使用疟疾寄生虫基因组数据库，并开发了新的资源来研究耐药性机制，寄生虫性发育过程中的基因调节以及寄生虫种群多样性和动态。朝这个方向的一个项目是通过数百个微卫星标记物的恶性疟原虫场分离株进行基因分型，以鉴定与耐药性相关的染色体基因座。全球90个寄生虫分离株的集合已带有342个标记，除了候选耐药性，有关寄生虫基因组结构，多样性，药物选择性扫描和进化关系的重要信息外，还揭示了除了候选基因座外。另一个项目是收集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。已经确定了各种候选基因。我们还正在开发大规模研究的资源，以包括：1）全基因组数据库，每个基因至少一个SNP与MS标记集成； 2）全球寄生虫分离株的集合； 3）。针对恶性疟原虫的单倍体基因组的统计和计算机计划。从四个寄生虫分离株中测序了染色体2和3上约400个基因，已经鉴定出数百个SNP。借助这些资源，我们可以专注于表型评估和测量，包括对各种抗疟疾和营养变化的寄生虫反应。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使用微阵列和蛋白质组学方法通过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研究寄生虫食品液泡中的蛋白质表达以及早期性发育的阶段。已经使用二维凝胶和质谱法鉴定了食物液泡的各种蛋白质和配子细胞发育的阶段。我们还使用源自寄生虫基因组的6300个寡核苷酸印刷了微阵列载玻片，并进行了一些初步杂交实验。鉴定候选基因后，将遵循详细的生化和遗传特征。