Genomics/Molecular Core

基因组学/分子核心

基本信息

批准号：
9263319
负责人：
Joana Carneiro da Silva
金额：
$ 7.85万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
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/9263319
关键词：
Anopheles Genus Antibody Response Archives Artemisinins Bangladesh Bioinformatics Biological Assay Blood Blood capillaries China Clinical Communities Country Culicidae Custom DNA DNA purification Data Data Set Databases Decision Trees Deposition Detection Development Diagnostic tests Dimensions Drug resistance Ensure Epidemiology Exposure to Falciparum Malaria Fingers Gene Expression Genetic Variation Genome Genomics Genotype Goals Haplotypes High-Throughput Nucleotide Sequencing Human Infection Intervention Laboratories Libraries Malaria Measures Methodology Modeling Molecular Molecular Epidemiology Myanmar National Institute of Allergy and Infectious Disease Nucleic Acids Parasitemia Parasites Pattern Peptides Pharmaceutical Preparations Plasmodium Plasmodium falciparum Plasmodium vivax Policies Polymerase Chain Reaction Procedures Production Proteins RNA Research Research Personnel Resistance Resources Reverse Transcription Sampling Science Scientist Serological Single Nucleotide Polymorphism Site Southeastern Asia Specimen Spottings System Techniques Technology Testing Time Variant Venous Work World Health Organization base density design genome sequencing genome-wide genomic data genomic epidemiology improved malaria infection migration milliliter multiplex detection next generation point of care portability public health intervention repository response success tool transmission process vector vector mosquito web portal web site whole genome

项目摘要

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. .

分子和基因组流行病学方法有潜力（目前尚未实现）增加我们已经在使用高度敏感的分子检测来消除疟疾。国家疟疾监测并指导缅甸的大规模药物管理。耐药性的出现和传播促使世界卫生组织发起了一项从东南亚消除恶性疟疾的区域运动。测量变体特异性抗体反应的微阵列可能对于估计暴露于特定寄生虫和蚊子种类的基因组测序和基因分型大量临床样本。产生可用于了解寄生虫迁移模式的信息。 Core 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、支持这些目标的基因组学和血清学技术和工具，重点是促进过渡在目标 1 中，我们建议在研究过程中向区域实验室提供大部分这些能力。在区域 ICEMR 实验室建立或加强高通量超灵敏 PCR 能力缅甸、中国和孟加拉国纳入新的反映多样性的微阵列血清监测在目标 2 中，我们将制定并实施测量疟疾和蚊子暴露的方法。在测序之前增加现场样本中寄生虫 DNA 的代表性。这些 DNA 样本将用于进行测序。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，并设计下一代 DNA 蛋白质和肽微阵列生成的数据将由这三个人进行分析。项目旨在准确估计该地区的真实疟疾负担，描述疟疾的特征耐药性的出现和传播，并将所有这些变量整合到疟疾区域模型中最后，目标 4 力求以流行病学和传播为基础进行公共卫生干预。通过使用公共数据存储库将生成的数据传播给更广泛的科学界以及针对特定项目的门户网站，以帮助指导国家和区域疟疾控制和消除政策。