Infectious Disease Genomics: Pathogen Evolution, Emergence, and Host Interaction

传染病基因组学：病原体进化、出现和宿主相互作用

• 批准号: 8836963
• 负责人: Bruce W. BIRREN
• 金额: $ 679.5万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8836963
• 关键词: Address; Animal Model; Biological Models; Biology; Candida albicans; Categories; Cells; Clinical; Communicable Diseases; Communities; Complex; Cryptococcus gattii; Dengue Virus; Developing Countries; Diagnosis; Disease Outbreaks; Economics; Evolution; Exposure to; Fever; Fusarium; Genomics; Immune response; Infection; Infectious Diseases Research; Insect Vectors; Insecticides; Instruction; Intervention; Knowledge; Laboratories; Lassa virus; Malaria; Measures; Methods; Monitor; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; Organism; Parasites; Pharmaceutical Preparations; Phenotype; Plasmodium falciparum; Population; Research; Research Personnel; Resources; Technology; Therapeutic; Training; Uropathogenic E. coli; Variant; Viral; Virulence; Virus; West Nile virus; Whole Organism; Work; analytical method; carbapenem-resistant Enterobacteriaceae; drug sensitivity; experience; member; microbial community; mortality; mutant; pathogen; prevent; response; social; tool; transmission process; vector mosquito

The staggering global toll taken by infectious diseases calls for vastly more effective monitoring, as well as new preventative and therapeutic measures. To address critical gaps in our knowledge about the basic biology of key pathogens and their interactions with their hosts and insect vectors, we will create a Genomic Center for Infectious Diseases (GCID). Our team combines an extensive track record of developing and applying groundbreaking laboratory and analytical methods with experience managing large and complex projects to produce resources for the infectious disease research community. We will use genomic methods to define the extent of variation among organisms, as well as among microbial communities. Our viral research will focus on the NIAID Category A priority pathogens Lassa and Dengue viruses, and the Category B priority pathogen West Nile virus, as well on surveillance for fever-causing viruses in tropical developing countries. Bacterial studies will focus on the Category C priority pathogens M. tuberculosis and Carbapenem-resistant Enterobacteriaceae, an emerging cause of nocosomial infections associated with high mortality, as well as the costly Uropathogenic E. coli. Fungal research will focus on major pathogens with significant clinical impact, C. neoformans and C. albicans, as well as strains causing recent fungal outbreaks, including C. gattii and Fusarium spp. We will also study both the malaria-causing parasite P. falciparum and its mosquito vector, A. gambiae. In studying these particular high-priority pathogens as model systems, we will produce, and train community members to use, new methods of wide utility. We will sequence natural isolates as well as laboratory-derived mutants, and associate sequence differences with phenotypes to help interpret the functional consequences of this variation with respect to virulence, transmission and drug sensitivity. Working at several levels, from populations to whole organisms, and animal models to single cells, we will reveal the long term (evolutionary) responses to pathogen and host interactions and exposure to drugs or insecticides as well as the immediate (transcriptional) responses of host and pathogens to infection. These responses define potential new opportunities for interventions to disrupt the cycle of infection and transmission. In bringing together outstanding investigators in infectious disease with cutting edge laboratory and analytical methods and experienced leaders in genomics, we will generate the information needed to create new tools to track, diagnose, treat and prevent infectious diseases.

传染病造成的惊人的全球死亡人数要求进行更有效的监测， 新的预防和治疗措施。为了弥补我们在基本知识方面的重大空白， 关键病原体的生物学及其与宿主和昆虫载体的相互作用，我们将创建一个基因组 传染病中心（GCID）。我们的团队结合了广泛的开发记录， 运用开创性的实验室和分析方法， 为传染病研究界提供资源的项目。我们将使用基因组方法 以确定生物体之间以及微生物群落之间的变异程度。我们的病毒 研究将集中在NIAID A类优先病原体拉沙病毒和登革热病毒，以及 B优先病原体西尼罗河病毒，以及对热带发展中国家发热病毒的监测 国家细菌研究将集中在C类优先病原体M。结核病和 耐碳青霉烯类肠杆菌科，一种新出现的与高水平 死亡率，以及昂贵的尿路致病性E。杆菌真菌研究将集中在主要病原体， 显著的临床影响，C.新型隐球菌和白色念珠菌，以及导致最近真菌爆发的菌株， 包括C. gattii和镰刀菌属（Fusarium spp.）我们还将研究引起疟疾的寄生虫恶性疟原虫和 其蚊媒A.冈比亚。在研究这些特定的高优先级病原体作为模型系统时，我们 将产生，并培训社区成员使用，广泛实用的新方法。我们会自然排序 分离株以及实验室衍生的突变体，并将序列差异与表型联系起来， 解释这种变异在毒力、传播和药物方面的功能后果 灵敏度从种群到整个生物体，从动物模型到单个 细胞，我们将揭示病原体和宿主相互作用和暴露的长期（进化）反应 以及宿主和病原体对药物或杀虫剂的直接（转录）反应， 感染这些应对措施为干预提供了潜在的新机会， 感染和传播。将传染病领域的杰出研究者与切割 先进的实验室和分析方法以及基因组学方面经验丰富的领导者，我们将产生 创建新工具以跟踪、诊断、治疗和预防传染病所需的信息。