Genomics Core

固有的信号通路可以调节流感病毒的复制，也有病毒对策，但我们对这些反应如何影响病毒疾病发病机制的认识仍然存在重大差距。 这一高度整合的计划的首要目标是使用基于系统的方法系统地解决这些问题，以揭示新的治疗方法。基因组学核心的目标是提供一个中心资源，促进流感病毒感染细胞的转录组(mRNA-Seq、Gro-Seq和纳米串基因表达分析)和表观基因组(ChlP-Seq)的高通量测序。该核心还将提供数据分析和集成，以揭示病毒-宿主转录反应网络。这些信息将被建模核心中的其他项目研究人员用来定义影响流感病毒感染的宿主分子网络和途径，并定义影响流感病毒疾病发病机制的罕见和破坏性基因多态(项目3)。与病毒-宿主转录反应网络有关的细胞网络、途径和基因将被RNAi敲除作为靶点，以确定系统中的扰动如何影响对野生型和特定突变的甲型流感病毒感染的转录反应网络。这些研究对于该项目的总体目标至关重要，该项目旨在揭示流感病毒对细胞功能以及关键抗病毒反应和病毒对策系统的全球影响。

Innate signaling pathways can regulate influenza virus replication, and there are viral countermeasures, but there remain critical gaps in our knowledge about how these responses impact viral disease pathogenesis. The overarching goal of this highly integrated program is to systematically address these questions using a systems-based approach to reveal new therapeutic approaches. The goal of the Genomics Core is to provide a central resource that will facilitate high throughput sequencing of the transcriptome (mRNA-seq, GRO-Seq, and Nanostring gene expression analysis) and the epigenome (ChlP-Seq) in influenza virus infected cells. The core will also provide data analysis and integration to uncover the virus-host transcriptional response network. This information will be used by other program investigators in the Modeling Core to define host molecular networks and pathways that impact influenza virus infection and to define rare and disruptive gene polymorphisms that influence influenza virus disease pathogenesis (Project 3). Cellular networks, pathways, and genes that are implicated in the virus-host transcriptional response network will be targeted by RNAi-knockdown to determine how perturbations in the system impact the transcriptional response network to infection by wild-type and specific mutant influenza A viruses. These studies are critical for the overall goal of the program aimed at uncovering the global effects of influenza virus on cellular functions and on the system of key antiviral responses and virus countermeasures.