Malaria Parasite Sexual Development, Drug Resistance

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来自恶性疟原虫染色体1、2、4、5、6、13和14上基因的额外单核苷酸多态性（SNP）。为了研究染色体单倍型、群体结构和重组率变异，我们还对来自全球99个分离株的3号染色体上的183个SNP进行了基因分型。目前正在分析这一数据集，以便发表。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。我们目前正在评估该基因的功能。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。

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 additional single nucleotide polymrphisms (SNPs) from genes on chromosome 1, 2, 4, 5, 6, 13 and 14 of Plasmodium falciparum. To study chromosomal haplotypes, population structures, and recombination rate variation, we have also genotyped 183 SNPs on chromosome 3 from 99 worldwide isolates. This data set is being analyzed for publication. We found that recombination rate vary 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 evaluating 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.