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

高通量基因组学和相关技术的出现已经提供了开始 问关于整个系统的生物学的详细问题，而不是检查系统的一部分， 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， 细菌、真菌和寄生虫病原体与来自人类受试者的独特样品组相关， 在可能的情况下，以及适当的疾病的动物模型，以每个项目。病原体通常 通过使用它们的基因产物来操纵细胞存活和复制的途径来破坏宿主细胞; 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作出反应。 破译这些复杂的时空动态，以确定新的毒力因子或宿主 反应途径对于充分理解传染病过程至关重要。的整合 生物学问题的高通量技术突出了基因组学作为一个领域的发展 从几年前的一个严格的观察工具，成为研究的一个组成部分， 检查疾病过程和整个人类健康。基因组学的观点变得越来越 完成，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。 从这些复杂的相互作用中获得的数据的整合为更深入的 了解健康和疾病。该提案包括一个高度合作的调查小组， 以马里兰州大学基因组科学研究所为中心，他们是 他们不仅是病原体生物学领域的专家，也是基因组学领域的先驱。我们预计这些 研究将解决与病毒、细菌、真菌 和寄生病原体以及宿主对感染的反应。

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.