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Omics for TB: Response to Infection and Treatment

结核病组学：对感染和治疗的反应

基本信息

批准号：
10339369
负责人：
ALAN A ADEREM
金额：
$ 334.54万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-12 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10339369
关键词：
Address Affect Bacteria Biological Cessation of life Clinical Collection Communicable Diseases Communities Complex Data Data Set Disease Disease Outcome Disease Progression Eicosanoids Elements Genetic Transcription Goals Human Immunologic Receptors Infection Inflammatory Response Infrastructure Mass Spectrum Analysis Methodology Modeling Molecular Profiling Mouse Strains Multiplexed Ion Beam Imaging Mus Mycobacterium tuberculosis Network-based Outcome Persons Pharmaceutical Preparations Phenotype Predisposition Proteomics Reagent Receptor Activation Records Research Research Personnel Resources Sampling Symptoms System Systems Analysis Systems Biology Technology Time Treatment outcome Tuberculosis Vaccines Work base biological heterogeneity chemotherapy combat cost effective data tools design drug-sensitive gene regulatory network global health emergency high risk in vivo lipidomics machine learning model member metabolomics mouse model network models novel pandemic disease pathogen predictive signature programs protein protein interaction response tool transcriptomics treatment response tuberculosis treatment

项目摘要

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.

摘要 – 概述结核病是一种全球健康问题，每年约有 1000 万新发活动性疾病病例和 180 万人死亡紧急情况。结核病的一个显着特征是其生物异质性，这体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相互竞争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反应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结核病进展的新宿主调节因子，以及他们控制的先天和适应性网络。我们还将寻求定义结核病治疗的新型结核病调节剂响应，以及他们控制的 Mtb 监管网络。这项工作将使我们能够生产和验证结核病进展和治疗反应的宿主和结核分枝杆菌模型。总而言之，该程序解决了阻碍抗击结核病大流行的努力的关键未解问题。我们的团队已经完善了需要平台和科学方法来及时且成本低廉地执行这一雄心勃勃的研究计划有效的方式。所有参与的研究人员都有良好的有效互动记录，并且向科学界传播他们的数据和试剂。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic Modification of Primary Human Myeloid Cells to Study Cell Migration, Activation, and Organelle Dynamics.

DOI：
10.1002/cpz1.514
发表时间：
2022-08
期刊：
Current protocols
影响因子：
0
作者：
Greiner, Daniel;Scott, Tiana M;Olson, Gregory S;Aderem, Alan;Roh-Johnson, Minna;Johnson, Jarrod S
通讯作者：
Johnson, Jarrod S

Experimental and Computational Workflow for RNA Sequencing in Mycobacterium tuberculosis : From Total RNA to Differentially Expressed Genes.

结核分枝杆菌 RNA 测序的实验和计算工作流程：从总 RNA 到差异表达基因。

DOI：
10.1007/978-1-0716-1460-0_21
发表时间：
2021
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Ma,Shuyi;JonesJr,RichardM;Gleason,NatalieS;Farrow-Johnson,Jessica;Sherman,DavidR
通讯作者：
Sherman,DavidR

The evolving biology of Mycobacterium tuberculosis drug resistance.