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Project Title:  Systems approach in a multi-organism strategy to understand biomolecular interactions in DOE-relevant organisms

Funding: U.S. Department of Energy, ENIGMA (Environment and Networks Integrated with Genomes and Molecular Assemblies)

Rational reengineering of biology for the purpose of bioremediation, bioenergy or C-sequestration requires deep understanding of all functional interactions of relevant components within native cell(s). Many of these functional interactions are conserved across diverse species to different degrees depending on their evolutionary distance. We are conducting integrative analysis of genomic architecture and composition, transcriptome and proteome structure/function, protein-protein and protein-DNA interactions and metabolic networks to find keystone complexes and specialized circuit architectures for important application-relevant genes.  These studies are readily generalizable to any organism as they are being developed using diverse organisms with important biological and evolutionary relevance to several DOE mission goals. Specifically, these organisms have enormous potentials from the standpoint of H2 production, N2 fixation, and C-sequestration; they include a heterotrophic halophile Halobacterium salinarum NRC-1, an anaerobic thermophile (Pyrococcus furiosus DSM 3638), an acidophilic and aerobic thermophile (Sulfolobus solfataricus P2); a hydrogenotrophic methanogen (Methanococcus maripaludis S2), and a photoheterotrophic halophile (Halobacterium salinarum NRC-1). In particular, we have developed an integrated systems approach to rapidly reverse engineer a gene regulatory network model (Environment & Gene Regulatory Influence Network, EGRIN) for any organism.  An EGRIN model can predict responses of an organism to endogenous and environmental stressors and can be used a powerful springboard to assign gene function, identify complexes, and rationally re-engineer networks for specific applications such as bioenergy and bioremediation.

You can reach computational and experimental results from this study and access all of the software tools developed in this project by visiting ENIGMA portal (

Gaggle software tools can be accessed at the Gaggle website and at the DOE/Archaea page.