Genomics/Molecular Core

分子和基因组流行病学方法有可能--大部分尚未实现--增加 为消除疟疾工具包提供强大的工具。我们已经在使用高度敏感的分子测试来 国家疟疾监测和指导缅甸的大规模药物管理。我们的单倍型分析 耐药性的出现和传播有助于促使世界卫生组织发起一项 消除东南亚恶性疟疾的区域运动。高通量蛋白质和多肽 测量变种特异性抗体反应的微阵列可能被证明对估计暴露于 特定的寄生虫和蚊子种类。大量临床标本的基因组测序和基因分型 产生可用于了解寄生虫迁移模式的信息。分子与基因组学 CORE将帮助项目1和项目2的研究人员开发和部署高灵敏度和高通量的分子， 支持这些目标的基因组学和血清学技术和工具，重点是促进过渡 在研究过程中，将这些能力中的大多数提供给区域实验室。在目标1中，我们建议 在ICEMR地区实验室建立或加强高通量超灵敏聚合酶链式反应能力 缅甸、中国和孟加拉国并纳入反映多样性的新的基于微阵列的血清监测 衡量疟疾和蚊子暴露的工具。在目标2中，我们将制定和实施以下方法 在测序前增加现场样本中寄生虫DNA的含量。这些DNA样本将被用来 在AIM 3中生成恶性疟原虫和间日疟原虫的高通量序列数据，并 设计下一代DNA、蛋白质和多肽微阵列。生成的数据将由这三个人进行分析 项目，以生成对该区域真实疟疾负担的准确估计，以确定 耐药性的出现和传播，并将所有这些变量整合到疟疾的区域模型中 流行病学和传播学，可作为公共卫生干预的依据。最后，目标4寻求 通过使用公共数据储存库，将生成的数据传播给更广泛的科学界 以及一个特定于项目的门户网站，以帮助指导国家和区域疟疾控制和消除政策。。

Molecular and genomic epidemiology approaches have the potential—as yet largely unrealized—to add powerful tools to the malaria elimination toolkit. We are already using highly sensitive molecular testing for national malaria surveillance and to guide mass drug administration in Myanmar. Our haplotype analyses of the emergence and dissemination of drug resistance helped prompt the World Health Organization to launch a regional campaign to eliminate falciparum malaria from Southeast Asia. High throughput protein and peptide microarrays that measure variant-specific antibody responses may prove valuable for estimating exposure to specific parasite and mosquito species. Genome sequencing and genotyping large numbers of clinical samples yields information that can be used to understand parasite migration patterns. The Molecular and Genomics Core will help Project 1 and 2 investigators develop and deploy high-sensitivity and high-throughput molecular, genomics and serological techniques and tools to support these goals, with a focus on facilitating the transition of most of these capabilities to regional laboratories over the course of the study. In Aim 1 we propose to establish, or strengthen capacity for, high-throughput ultrasensitive PCR at regional ICEMR laboratories in Myanmar, China and Bangladesh and incorporate new diversity-reflecting microarray-based sero-surveillance tools to measure malaria and mosquito exposure. In Aim 2, we will develop and implement approaches to increase parasite DNA representation in field samples prior to sequencing. These DNA samples will be used to generate high-throughput sequence data for Plasmodium falciparum and Plasmodium vivax in Aim 3, and to design next-generation DNA protein and peptide microarrays. The data generated will be analyzed by all three Projects, to generate accurate estimates of the true malaria burden in the region, to characterize the emergence and spread of drug resistance, and to integrate all these variables into a regional model of malaria epidemiology and transmission, upon which public health interventions can be based. Finally, Aim 4 seeks to disseminate the generated data to the wider scientific community, though the use of public data repositories and a project-specific web portal, to help guide national and regional malaria control and elimination policies. .