Bilateral BBSRC-NSF/BIO: Identifying Mechanisms for Environmental Adaptation in Bacteria

这个合作项目邀请了美国(系统生物学研究所)和英国(伯明翰大学)的研究人员，以加强对基因调控如何演变以及在一组相关但仍不同的微生物中发挥作用的理解。关于CMNR细菌(棒状杆菌、分枝杆菌、诺卡菌和红球菌)如何适应新环境的知识将被用于改善它们在修复污染物、生产生物能源和改善公众健康方面的使用。CMNR细菌生活在土壤中，与植物合作，包括许多行业非常感兴趣的微生物和病原体。该项目的研究人员将检验一种假设，即这类细菌定居的栖息地的多样性源于它们通过改变细胞膜中复杂脂肪分子的排列来适应新环境的能力。这项研究还将扩展美国团队开发的高中教育课程，该课程使用系统的方法来探索全球粮食安全问题。将纳入模拟自然粮食生产系统的活动，并使用网络模型研究生态系统动力学、功能和复原力。该课程将与下一代科学标准(美国)和国家课程(英国)的目标保持一致。该课程将通过一个被广泛访问的教育网站广泛传播到美国和英国的教室。即将开发的计算工具和实验方法将对广泛的研究社区有用，并将作为有充分文件记录的开源资源提供。CMNR细菌通过使用不同组合的并列酶来选择性地分解不同的底物并改变其细胞膜的组成，从而适应不同的生境。为了阐明CMNR细菌的这一组合策略，将使用系统生物学方法对耻垢分枝杆菌内潜在的条件活性基因调控网络进行逆向工程。对所有CMNR细菌基因组的比较分析将有助于推断基因调控网络，并有助于阐明网络在进化上保守和独特的特征。此外，通过将污垢分枝杆菌模型在不同底物和环境条件之间生长过渡期间模块结构的变化关联起来，将确定影响细胞被膜组成特定变化的基因和子网络内的相互作用。模型预测将通过分析相关条件下特定基因缺失对具有代表性的CMNR细菌细胞膜成分的后果来验证。该项目将产生创新的方法，以构建和分析跨相关但不同的微生物的基因调控网络模型。这一美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究理事会的支持。

This collaborative project engages researchers in the US (Institute for Systems Biology) and the UK (University of Birmingham) to enhance understanding of how gene regulation has evolved and functions across a group of related but nevertheless diverse microorganisms. Knowledge of how CMNR bacteria (Corynebacterium, Mycobacterium, Nocardia and Rhodococcus) adapt to new environments will be used to improve their use in remediating pollutants, producing bioenergy, and improving public health. CMNR bacteria inhabit soils, cooperate with plants, and include microbes and pathogens that are of great interest to many industries. The investigators in this project will examine the hypothesis that the diversity of habitats colonized by this group of bacteria is rooted in their ability to adapt to new environments by altering the arrangement of complex fat molecules in their cell envelope. The research will also expand the high school educational curriculum developed by the US team, which uses a systematic approach to explore the global issue of food security. Activities will be incorporated that model natural food production systems and that use network models to study ecosystem dynamics, functioning, and resilience. The curriculum will be aligned with the goals of the Next Generation Science Standards (US) and National Curriculum (UK). The curriculum will be widely disseminated to classrooms in the US and UK through a widely accessed education website. The computational tools and experimental methods to be developed will be useful to the broad research community and will be made available as well-documented, open-source resources.CMNR bacteria adapt to diverse habitats by using paralogous enzymes in different combinations to selectively catabolize different substrates and alter the composition of their cell envelope. To elucidate this combinatorial strategy of CMNR bacteria, the underlying conditionally active gene regulatory networks within Mycobacterium smegmatis will be reverse engineered using a systems biology approach. Comparative analysis across all CMNR bacterial genomes will facilitate inference of the gene regulatory networks and also aid in elucidating the evolutionarily conserved and unique features of the networks. Further, genes and interactions within sub-networks that effect specific changes in cell envelope composition will be identified by correlating changes in modular architecture of the M. smegmatis model during growth transitions between varying substrates and environmental conditions. Model predictions will be tested by analyzing consequences of specific gene deletions on cell envelope composition of representative CMNR bacteria under relevant conditions. This project will generate innovative approaches to construct and analyze a gene regulatory network model across related, but distinct, microorganisms. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.