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

传染病造成的令人震惊的全球损失要求更有效的监测以及 新的预防和治疗措施。解决我们在基本知识方面的严重差距 关键病原体的生物学及其与宿主和昆虫媒介的相互作用，我们将创建一个基因组 传染病中心(GCID)。我们的团队结合了开发和开发的广泛记录 应用开创性的实验室和分析方法，具有管理大型和复杂系统的经验 为传染病研究社区提供资源的项目。我们将使用基因组方法 以确定有机体之间以及微生物群落之间的差异程度。我们的病毒 研究将集中在NIAID A类优先病原体Lassa和Dengue病毒，以及 B优先病原体西尼罗河病毒，以及热带发展中致热病毒的监测 国家。细菌研究将集中在C类优先病原体结核分枝杆菌和 耐碳青霉烯类肠杆菌科细菌与高致病性医院感染相关的新病原菌 死亡率，以及代价高昂的致尿性大肠杆菌。真菌研究将集中在主要病原体和 重大临床影响，新生葡萄球菌和白色念珠菌，以及导致最近真菌暴发的菌株， 包括赤霉菌(C.gattii)和镰刀菌(Fusum spp.)我们还将研究导致疟疾的寄生虫恶性疟原虫和 它的蚊子媒介冈比亚按蚊。在研究这些特殊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。我们将按自然顺序排列 分离以及实验室衍生的突变体，并将序列差异与表型相关联，以帮助 解释这种变异在毒力、传播和药物方面的功能后果 敏感度。从种群到整个生物体，从动物模型到单个动物，在几个层面上工作 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 对药物或杀虫剂的反应以及寄主和病原体对 感染。这些应对措施为干预定义了潜在的新机会，以扰乱 感染和传播。将传染病和切割领域的杰出研究人员聚集在一起 EDGE实验室和分析方法，以及在基因组学方面经验丰富的领导者，我们将产生 创建跟踪、诊断、治疗和预防传染病的新工具所需的信息。

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.