Pathway Analysis in Tuberculosis

结核病通路分析

• 批准号: 10024699
• 负责人: SABINE EHRT
• 金额: $ 263.97万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-12 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10024699
• 关键词: Adult; Affect; Anabolism; Antibiotics; Bacteria; Biochemical; Biochemistry; Bioinformatics; Biological Assay; Biology; Biotin; Cell Wall; Cell division; Collaborations; Complex; Data Analyses; Degradation Pathway; Development; Disease; Drug resistance; Environment; Enzymatic Biochemistry; Enzymes; Epidemic; Evolution; Fatty Acids; Genes; Genetic; Goals; Growth; Infection; Lipids; Mediating; Metabolic; Metabolism; Methodology; Methods; Modality; Molecular; Multi-Drug Resistance; Mutation; Mycobacterium tuberculosis; New Agents; Pathway Analysis; Pathway interactions; Pharmaceutical Preparations; Phenotype; Play; Post-Transcriptional Regulation; Process; Proteins; RNA; RNA Degradation; RNA Processing; Research; Research Personnel; Resources; Role; Stress; Structure; System; Techniques; Therapeutic; Thinking; Treatment Efficacy; Tuberculosis; Ursidae Family; Virulence; Work; cofactor; complex biological systems; data dissemination; data sharing; genetic approach; global health; innovation; large scale data; lipid biosynthesis; metabolomics; mycobacterial; pathogen; programs; protein protein interaction; response; small molecule; stressor; synergism

Overall, Abstract Despite the availability of therapy, Mycobacterium tuberculosis (Mtb) is the major infectious killer of adults. Finding more effective therapeutic strategies will require a better understanding of the fundamental biology of bacterial growth, metabolism and interaction with the host. This program proposes to understand key pathways in Mtb biology using advanced genetic and biochemical methods, with a particular focus on complex pathways important in adaptation to disease-relevant stressors. “Pathways” is defined broadly, including biochemical, structural and genetic interactions. In many cases, traditional genetic approaches to discover and understand these pathways are limited, but many of the most critical aspects of Mtb biology are mediated by such complex genetic mechanisms. This program will leverage new methodology and resources that the collaborators have developed in the last few years, to discover the constituents of key pathways, attribute functions to new pathways, and understand the mechanisms which underlie the ability of bacteria to survive and grow under a variety of conditions, focusing on those encountered during infection. They will also take advantage of the close collaborations among the investigators who have worked well together for several years. The work will be organized into four projects and four cores, but considerable crossover is expected, which will enrich each component. Project 1. Metabolic adaptations required for growth and virulence of Mtb at acidic pH. Project 2. Acquisition, synthesis and importance of biotin in Mtb. Project 3. Defining the RNA processing and degradation pathways of Mtb. Project 4. Defining cell division pathways in Mtb. Core A. Metabolomics and lipidomics. Core B. Biochemistry and enzymology. Core C. Bioinformatics and data sharing. Core D. Administration. All of this work will be facilitated by a highly collaborative group of investigators, almost all of whom have worked together for many years on a large variety of projects. Both project and core investigators will serve as full- fledged intellectual contributors, enabling the team to bring a variety of approaches and thinking to bear on complex biological systems.

总体而言，抽象 尽管有治疗的可用性，但结核分枝杆菌（MTB）是成年人的主要传染性杀手。 寻找更有效的治疗策略将需要更好地了解 细菌生长，代谢和与宿主的相互作用。该计划的建议了解关键途径 在MTB生物学中使用先进的遗传和生化方法，特别关注复杂 途径对于适应与疾病相关的压力源很重要。 “途径”的定义广泛，包括 生化，结构和遗传相互作用。在许多情况下，传统的遗传方法发现和 了解这些途径是有限的，但是MTB生物学的许多最关键方面是由 这种复杂的遗传机制。该程序将利用新的方法和资源 在过去的几年中，合作者开发了，以发现关键途径的构成，属性 发挥新途径的功能，并了解细菌生存能力的基础的机制 在各种疾病下生长，重点是感染期间遇到的疾病。他们也会利用 在工作已经有好几年的调查人员之间的密切合作中。工作 将组织成四个项目和四个核心，但预计会有很大的跨界 成分。 项目1。在酸性pH时MTB生长和病毒所需的代谢适应性。 项目2。生物素在MTB中的获取，合成和重要性。 项目3。定义MTB的RNA处理和降解途径。 项目4。定义MTB中的细胞分裂途径。 核心A.代谢组学和脂质组学。 核心B.生物化学和酶学。 核心C.生物信息学和数据共享。 核心D.管理。 所有这些工作都将由高度协作的调查人员组成，几乎所有人都在工作 多年来在各种项目上共同多年。项目和核心调查人员都将成为 逃离的知识分子贡献者，使团队能够带来各种方法并考虑 复杂的生物系统。