Malaria Parasite Sexual Development and Drug Resistance

疟疾寄生虫的性发育和耐药性

• 批准号: 7196685
• 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/7196685
• 关键词: Plasmodium; Plasmodium falciparum; antibody; biochemical evolution; communicable disease control; communicable disease transmission; developmental genetics; drug resistance; gene expression; genetic polymorphism; genetic regulation; immunotherapy; malaria; malaria vaccines; microarray technology; microorganism culture; microorganism growth; nonhuman therapy evaluation; nucleic acid sequence; population genetics; protozoal genetics; reproductive development; single nucleotide polymorphism; vaccine development

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. Building on progress made last year, we have now collected single nucleotide polymorphisms (SNPs) from genes (~5000) on all of the 14 chromosomes of Plasmodium falciparum. We are currently working to develop a platform that will allow us to genotype large number of SNPs. We also have an IRB protocol approved for collecting parasites from field sites in Cambodia. To study chromosomal haplotypes, population structures, and recombination rate variation, we genotyped 183 SNPs on chromosome 3 from 99 worldwide isolates. We found that recombination rate varied greatly among parasite populations and across chromosome 3. We have also finished sequencing 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. 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. Phenotypic changes are being evaluated after genetic knockout of the target gene. We are currently studying the function of the gene. Monoclonal antibodies against gametocyte were produced, and the target proteins recognized by the antibodies are being identified. The potential of the antibodies in blocking transmission are also being tested.

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进化。在去年取得进展的基础上，我们现在已经收集了恶性疟原虫所有14条染色体上基因（约5000个）的单核苷酸多态性（SNP）。 我们目前正在开发一个平台，使我们能够对大量SNP进行基因分型。我们也有一个IRB协议批准从柬埔寨的现场收集寄生虫。 为了研究染色体单倍型、群体结构和重组率变异，我们对来自全球99个分离株的3号染色体上的183个SNP进行了基因分型。我们发现寄生虫种群之间和3号染色体上的重组率差异很大。我们还完成了176个间日疟原虫分离株和5个其他灵长类疟疾物种的线粒体基因组测序。我们的数据支持宿主转换假说和间日疟原虫起源于亚洲猴。 我们实验室的另一个主要努力是研究与寄生虫性分化相关的基因表达和调控。我们已经确定了一个基因，可能发挥关键作用的配子体发育，使用微阵列和遗传图谱。在基因敲除靶基因后，正在评估表型变化。我们目前正在研究该基因的功能。制备了抗配子体的单克隆抗体，并对抗体识别的靶蛋白进行了鉴定。抗体阻断传播的潜力也正在测试中。