Mycobacteriophage as an emerging model organism

分枝杆菌噬菌体作为一种新兴的模式生物

• 批准号: 8260348
• 负责人: Graham F. Hatfull
• 金额: $ 28.61万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260348
• 关键词: Address; Animal Model; Bacteriophages; Biochemistry; Biological; Biological Models; Biological Process; Biology; Cloning Vectors; Collaborations; Collection; Communities; Data; Databases; Development; Education; Event; Evolution; Faculty; Fostering; Gene Expression; Gene Expression Profile; Gene Structure; Generations; Genes; Genetic; Genetic Variation; Genome; Genomics; Genus Mycobacterium; Goals; Human; Infectious Agent; Institution; Investigation; Knock-out; Length; Letters; Location; Maintenance; Methods; Molecular Biology; Mutagenesis; Mycobacteriophages; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nature; Online Systems; Plasmid Cloning Vector; Population; Regulation; Regulatory Element; Research; Research Personnel; Resource Development; Resources; Schools; Sequence Analysis; Students; System; Technology; Time; Tuberculosis; Universities; Virus; base; college; data sharing; expression cloning; gene function; genetic manipulation; genetic resource; genome database; killings; knockout gene; mutant; mycobacterial; particle; programs; promoter; protein folding; protein structure function; public health relevance; repository; research study; science education; tool; transcriptomics; undergraduate student; web site

DESCRIPTION (provided by applicant): Mycobacteriophages are emerging as a premiere model system for understanding fundamental questions In gene expression, protein structure and function, and genome evolution. Mycobacteriophages are viruses that infect mycobacteria, and are easy to Isolate, grow, and genomically characterize. Over 100 mycobacteriophage genomes have been sequenced - the largest group of phages infecting a single common host - but a tiny fraction of the global population of 1031 particles dominating the biosphere. Mycobacteriophages are amazingly diverse and 85% of their genes are of unknown function. Elucidating gene functions and unraveling the biological secrets of the mycobacteriophages has not been possible for lack of a system for genetic manipulations to make gene knockouts, insertions, and to add gene tags. This problem was circumvented with development of BRED technology for genome manipulation. For the first time, development of a facile and broadly applicable mycobacteriophage genetic system is possible. With nearly 10,000 genes, mostly of unknown function, there is an emerging and critical need for these tools. While the number of mycobacteriophage researchers has been fairly modest, it is currently exploding because of two main events. First is the implementation of mycobacteriophage discovery and genomics by the HHMI Science Education Alliance in colleges and universities across the US, with inclusion by 2011 of 36 institutions, 75 faculty, and many hundreds of student researchers, many who need to extend their investigations to address specific questions in mycobacteriophage biology and need the tools to do so. Secondly, the simplicity of the new BRED technology makes it generally applicable. The genetic tools we will develop will enable construction of simple unmarked gene knockouts, gene essentiality determination, creation of insertion mutants and tagged genes, and s transposition mutagenesis systems. We will also generate resources including phage-specific primers, plasmid vectors, and transcriptome data. The phagesdb.org web site will provide a central location for mycobacteriophage genome data, dissemination of resources, material requests, establishment of collaborations, and sharing of materials. PUBLIC HEALTH RELEVANCE: Mycobacteriophages offer new paradigms for gene function, expression and regulation, as well as understanding the mechanisms of genome evolution. In addition to being a simple and powerful model organism, they also provide powerful tools for understanding their host, Mycobacterium tuberculosis, which kills more people than any other single infectious agent.

描述（由申请人提供）：分枝杆菌正在成为一种首映模型系统，用于了解基因表达，蛋白质结构和功能以及基因组进化中的基本问题。分枝杆菌是感染分枝杆菌并且易于分离，生长和基因组的病毒。已经对超过100个分枝杆菌基因组进行了测序，这是感染单个普通宿主的最大噬菌体 - 但在占主导地位的1031个颗粒的全球群体中，一小部分。分枝杆菌噬菌体具有惊人的多样性，其85％的基因具有未知的功能。阐明基因功能并阐明分枝杆菌的生物学秘密是由于缺乏遗传操作的系统来制造基因敲除，插入和添加基因标签的系统。通过开发用于基因组操纵的育种技术的发展，这个问题得到了规避。首次可以开发便捷且广泛适用的分枝杆菌遗传系统。有近10,000个基因，主要是未知功能，因此对这些工具有一个新兴和迫切的需求。虽然分枝杆菌研究人员的数量相当适中，但由于两个主要事件，目前正在爆炸。首先是HHMI科学教育联盟在美国的大学和大学中实施分枝杆菌发现和基因组学，到2011年的36个机构，75名教职员工以及许多学生研究人员，许多人需要扩展他们的研究以解决mycobacteriophage Biogogage Biology和需要工具的特定问题。其次，新的育种技术的简单性使其通常适用。我们将开发的遗传工具将能够构建简单的未标记基因敲除，基因本质性确定，插入突变体和标记基因的创建以及S转位诱变系统。我们还将生成资源，包括噬菌体特异性引物，质粒向量和转录组数据。 phagesdb.org网站将为分枝杆菌基因组数据，资源传播，材料请求，合作建立和共享材料提供一个中心位置。 公共卫生相关性：分枝杆菌为基因功能，表达和调节提供了新的范式，并了解基因组进化的机制。除了成为一种简单而强大的模型生物外，它们还提供了强大的工具来理解其宿主结核分枝杆菌，这比任何其他单一的感染剂都杀死了更多的人。