Omics for TB: Response to Infection and Treatment

摘要-概述 每年约有1000万新发活动性疾病病例和180万例死亡，结核病是一个全球性的健康问题， 紧急情况结核病的一个显著特征是其生物学异质性，这表现在临床上， 水平主要有两种形式：疾病进展和治疗反应。该计划的前提是， 结核病感染和治疗的异质性结果是由竞争因素的相互作用决定的， 病原体和宿主之间的调节网络。我们的主要目标是应用系统生物学 阐明疾病结果和对疾病反应的变异性背后的生物控制的方法 治疗我们的第一个具体目标是定义体内TB疾病进展的新宿主调节因子， 它们控制的先天和适应性网络。我们还将寻求确定结核病治疗的新型结核杆菌调节剂 反应，以及他们控制的结核分枝杆菌监管网络。这项工作将使我们能够生产和验证 宿主和结核分枝杆菌模型的结核病进展和治疗反应。总而言之，该计划解决了 阻碍结核病大流行努力的关键未解问题。我们的团队已经完善了 所需的平台和科学方法，以执行这一雄心勃勃的研究计划，及时和成本- 有效的方式。所有参与的研究者都有很好的互动记录， 向科学界传播他们的数据和试剂。

Abstract – Overview With about 10 million new cases of active disease and 1.8 million deaths annually, TB is a global health emergency. A distinguishing feature of TB disease is its biological heterogeneity, which manifests at the clinical level chiefly in 2 forms: disease progression and treatment response. The premise of this Program is that the heterogeneous outcomes of TB infection and treatment are determined by the interplay of competing regulatory networks between the pathogen and the host. Our primary goal is to apply systems biology approaches to elucidate the biological control underlying the variability of disease outcome and response to treatment. Our first specific aim is to define novel host regulators of TB disease progression in vivo, and the innate and adaptive networks they control. We will also seek to define novel Mtb regulators of TB treatment response, and the Mtb regulatory networks that they control. This work will allow us to produce and validate host and Mtb models of TB disease progression and treatment response. Altogether, this program addresses key unanswered questions that stymie efforts to combat the TB pandemic. Our team has perfected the required platforms and scientific approaches to execute this ambitious research plan in a timely and cost- effective manner. All the participating investigators have strong records of interacting productively, and of disseminating their data and reagents to the scientific community.