Genomics/Molecular Core

分子和基因组流行病学方法有可能--但在很大程度上尚未实现--增加 疟疾消除工具包的强大工具。我们已经在使用高灵敏度的分子检测， 在缅甸，该项目旨在加强国家疟疾监测，并指导大规模药物管理。我们的单倍型分析 抗药性的出现和传播促使世界卫生组织发起了一项 在东南亚消灭恶性疟疾的区域运动。高通量蛋白质和肽 测量变异体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。对大量临床样本进行基因组测序和基因分型 产生的信息可用于了解寄生虫迁移模式。分子与基因组学 核心将帮助项目1和2的研究人员开发和部署高灵敏度和高通量的分子， 基因组学和血清学技术和工具，以支持这些目标，重点是促进过渡 在研究过程中，将这些能力中的大部分提供给区域实验室。在目标1中，我们建议 在区域ICEMR实验室建立或加强高通量超灵敏PCR能力， 缅甸、中国和孟加拉国，并纳入新的反映多样性的微阵列血清监测 测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： 在测序之前增加田间样品中寄生虫DNA的代表性。这些DNA样本将用于 在目标3中生成恶性疟原虫和间日疟原虫的高通量序列数据，以及 设计下一代DNA蛋白质和肽微阵列。所产生的数据将由三家公司进行分析 项目，以准确估计该区域的真正疟疾负担， 抗药性的出现和传播，并将所有这些变量纳入疟疾区域模型 流行病学和传播，公共卫生干预措施可以以此为基础。第四，目标是 通过使用公共数据储存库，向更广泛的科学界传播生成的数据 以及一个针对具体项目的门户网站，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. .