Host, Pathogen, and the Microbiome: Determinants of Infectious Disease Outcome

宿主、病原体和微生物组：传染病结果的决定因素

• 批准号: 9038240
• 负责人: CLAIRE M. FRASER
• 金额: $ 390.55万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038240
• 关键词: Address; Animal Disease Models; Area; Biological; Biology; Cells; Communicable Diseases; Communities; Complex; Diagnostic; Disease; Disease Outcome; Environment; Evolution; Foundations; Gene Expression; Genome; Genomics; Goals; Health; Human; Immune response; Immune system; Infection; Institutes; Instruction; Invaded; Knowledge; Maryland; Molecular; Morbidity - disease rate; Pathway interactions; Process; Published Comment; Research; Research Personnel; Sampling; Science; System; Technology; Universities; Vaccines; Viral; Viral Pathogenesis; Virulence Factors; Work; antimicrobial; base; data integration; design; gene product; high throughput technology; human subject; microbiome; microbiota; mortality; novel; pathogen; tool

The advent of high-throughput genomics and associated technologies have afforded the ability to begin to ask detailed questions about the biology of whole systems, rather than examining parts of the system in isolation. This application contains studies that explore the dynamic interactions between pathogens, hosts, their microbiota, the immune system, and the environment, with the goal to provide a more comprehensive understanding of the determinants of infectious disease outcome. The projects target high priority viral, bacterial, fungal, and parasitic pathogens in relation to unique sets of samples from human subjects, when possible, as well as relevant animal models of disease, as appropriate to each project. Pathogens often subvert host cells by using their gene products to manipulate cellular pathways for survival and replication; in turn, host cells respond to the invading pathogen through cascading changes in gene expression. Deciphering these complex temporal and spatial dynamics to identify novel virulence factors or host response pathways is essential for full understanding of the infectious disease process. The integration of the high-throughput technology with the biological question highlights the evolution of genomics as an area of research from a strictly observational tool of only a few years ago, to being an integral part in the examination of the disease process and human health as a whole. The genomic viewpoint is becoming more complete, as we can begin to simultaneously characterize the interactions of host, pathogen and microbiota. The integration of the data from these complex interactions is providing the foundation for a deeper understanding of health and disease. This proposal includes a highly collaborative group of investigators centered within the Institute for Genome Sciences at the University of Maryland who are experts in their respective areas of pathogen biology, but also are pioneers in the field of genomics. We expect that these studies will address major gaps in knowledge related to the molecular pathogenesis of viral, bacterial, fungal and parasitic pathogens and in host responses to infection.

高通量基因组学和相关技术的出现使我们能够开始 询问有关整个系统生物学的详细问题，而不是检查系统的某些部分 隔离。该应用程序包含探索病原体、宿主、 他们的微生物群、免疫系统和环境，目标是提供更全面的 了解传染病结果的决定因素。这些项目针对高优先级病毒、 与人类受试者的独特样本组相关的细菌、真菌和寄生病原体，当 可能的，以及相关的疾病动物模型，视每个项目而定。病原体经常 通过利用宿主细胞的基因产物来操纵细胞的生存和复制途径来颠覆宿主细胞；在 反过来，宿主细胞通过基因表达的级联变化对入侵的病原体做出反应。 破译这些复杂的时空动态以识别新的毒力因子或宿主 反应途径对于充分了解传染病过程至关重要。的整合 解决生物学问题的高通量技术凸显了基因组学作为一个领域的演变 研究从几年前的严格观察工具，发展成为研究的一个组成部分 对疾病过程和人类健康的整体检查。基因组学观点越来越多 完整的，因为我们可以开始同时表征宿主、病原体和微生物群的相互作用。 来自这些复杂交互的数据的集成为更深入的分析提供了基础 对健康和疾病的了解。该提案包括一个高度协作的研究小组 以马里兰大学基因组科学研究所为中心，他们是各自领域的专家 各自领域的病原体生物学，同时也是基因组学领域的先驱。我们期望这些 研究将解决与病毒、细菌、真菌的分子发病机制相关的知识的主要空白 和寄生病原体以及宿主对感染的反应。