Systematic mutagenesis of the model organism Streptomyces coelicolor: completion of an essential resource for the research community

模式生物天蓝色链霉菌的系统诱变：完成研究界的重要资源

• 批准号: BB/E019242/1
• 负责人: Paul Dyson
• 金额: $ 27.85万
• 依托单位: Swansea University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE019242%2F1
• 关键词: Systematic; mutagenesis; model; organism; Streptomyces

Streptomyces are fascinating soil bacteria of major economic importance as they produce 70% of antibiotics known to man. Unusually for bacteria, they exhibit a complex differentiating life-cycle that has implications for antibiotic production. Due to their importance, the BBSRC and Wellcome Trust funded the complete genome sequencing of the model species S. coelicolor. As a consequence, we know this bacterium possesses about 8000 genes. However, as yet we only understand the biological function of a small proportion of these genes. Understanding gene function is important as it enables us to learn more about the biology of Streptomyces and, in particular, the complexities of the regulation of antibiotic production and differentiation. In addition, S. coelicolor is a genetically tractable model to understand conserved processes it shares with important human pathogens such as Mycobacterium tuberculosis. A critical aspect of understanding gene function is the creation of mutants in which a specific gene is no longer active. By comparing characteristics of the mutant with those of a non-mutant, it is possible to learn about the function of the gene in question. The proposed research intends to complete the construction of a versatile resource that is currently being used by researchers worldwide to create specific gene mutations in S. coelicolor. This resource is made by insertion of a 'jumping gene' or transposon into the DNA sequence of each S. coelicolor gene. These insertions are made in gene copies cloned in a cosmid library: this library was used to obtain the S. coelicolor genome sequence. So for each original cosmid carrying approximately 30 contiguous genes, we construct a sub-library consisting of individual cosmids each carrying an individual insertion in each gene. With access to these mutant cosmids, researchers can easily construct a S. coelicolor mutant defective in a gene of interest. Information on the systematic cosmid mutagenesis programme is accessible to any researcher via an online database, allowing them to select and order specific mutant cosmids for their own use. In addition, we will ourselves use the resource to investigate in more detail how Streptomyces adapt to the varying moisture content of their natural environment. This itself impacts on the life-cycle and antibiotic production.

链霉菌具有引人入胜的土壤细菌，具有主要的经济重要性，因为它们产生了人类已知的70％的抗生素。对于细菌而言，它们异常地表现出复杂的分化生命周期，对抗生素产生具有影响。由于其重要性，BBSRC和Wellcome Trust资助了模型物种S. coelicolor的完整基因组测序。结果，我们知道该细菌具有约8000个基因。但是，到目前为止，我们只了解这些基因一小部分的生物学功能。了解基因功能很重要，因为它使我们能够更多地了解链霉菌的生物学，尤其是抗生素生产和分化的复杂性。此外，Coelicolor是一种可理解与重要人类病原体（如结核分枝杆菌）共享的遗传障碍模型。理解基因功能的一个关键方面是突变体的创建，其中特定基因不再活跃。通过将突变体的特征与非突变体的特征进行比较，可以了解有关基因的功能。拟议的研究旨在完成全球研究人员目前正在使用多功能资源的构建，以在S. coelicolor中创建特定的基因突变。该资源是通过将“跳跃基因”或转座子插入到每个Coelicolor基因的DNA序列中的。这些插入是用克隆在宇宙文库中的基因副本进行的：该文库用于获得卵形链球菌基因组序列。因此，对于每个带有大约30个连续基因的原始宇宙，我们构建了一个亚图木，由每个基因中的单个宇宙组成。通过访问这些突变体宇宙，研究人员可以轻松地在感兴趣的基因中构造卵形链球菌突变体有缺陷。任何研究人员都可以通过在线数据库访问有关系统的宇宙诱变程序的信息，从而使他们可以选择并订购特定的突变体宇宙供自己使用。此外，我们将自己利用资源更详细地研究链霉菌如何适应其自然环境中不同的水分含量。这本身会影响生命周期和抗生素产生。

项目成果

Reference Module in Biomedical Sciences

生物医学科学参考模块

• DOI: 10.1016/b978-0-12-801238-3.02306-0
• 发表时间: 2014
• 作者: Dyson P

The evolution of an osmotically inducible dps in the genus Streptomyces.

• DOI: 10.1371/journal.pone.0060772
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Facey PD;Hitchings MD;Williams JS;Skibinski DO;Dyson PJ;Del Sol R
• 通讯作者: Del Sol R

Cell-Biological Studies of Osmotic Shock Response in Streptomyces spp.

• DOI: 10.1128/jb.00465-16
• 发表时间: 2017-01-01
• 期刊: JOURNAL OF BACTERIOLOGY
• 影响因子: 3.2
• 作者: Fuchino, Katsuya;Flardh, Klas;Ausmees, Nora
• 通讯作者: Ausmees, Nora

The dpsA gene of Streptomyces coelicolor: induction of expression from a single promoter in response to environmental stress or during development.

• DOI: 10.1371/journal.pone.0025593
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Facey PD;Sevcikova B;Novakova R;Hitchings MD;Crack JC;Kormanec J;Dyson PJ;Del Sol R
• 通讯作者: Del Sol R

A novel bifunctional histone protein in Streptomyces: a candidate for structural coupling between DNA conformation and transcription during development and stress?

• DOI: 10.1093/nar/gkt180
• 发表时间: 2013-05
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Aldridge M;Facey P;Francis L;Bayliss S;Del Sol R;Dyson P
• 通讯作者: Dyson P