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使我们有能力开始 询问有关整个系统生物学的详细问题，而不是在 与世隔绝。该应用程序包含探索病原体、宿主、 他们的微生物区系、免疫系统和环境，目标是提供更全面的 了解传染病结局的决定因素。这些项目的目标是高优先级的病毒， 细菌、真菌和寄生虫病原体与来自人类受试者的独特样本集相关，当 可能的，以及相关的动物疾病模型，视每个项目而定。病原体经常 通过使用宿主细胞的基因产物来操纵细胞存活和复制的途径来颠覆宿主细胞； 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做出反应。 破译这些复杂的时间和空间动态以识别新的毒力因素或宿主 反应途径对于充分理解传染病的过程是至关重要的。整合了 具有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进化 研究从仅仅几年前的一个严格的观察工具，到成为 对疾病过程和人类整体健康的检查。基因组学观点正在变得越来越多 完成，因为我们可以开始同时表征宿主、病原体和微生物区系之间的相互作用。 来自这些复杂交互的数据的集成正在为更深层次的 对健康和疾病的理解。这项提议包括一个高度合作的调查小组 中心位于马里兰大学基因组科学研究所，他们是 病原体生物学的各个领域，但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、真菌的分子发病机制相关的主要知识空白 以及寄生病原体和宿主对感染的反应。

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.