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.<br/><br/>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. <br/><br/>This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.