High-throughput genome sequencing of microbes, plants, and complex environmental assemblages of organisms has provided the vital blueprint necessary to understand the functional potential of organisms and interactive communities. By examining the translation of genetic codes into integrated networks of regulatory elements, catalytic proteins, and metabolic networks that define all living organisms, systems biology research sheds light on the fundamental principles that govern functional properties of organisms and how their processes respond to community interactions and environmental variables.
The Department of Energy (DOE) Genomic Science program supports systems biology research aimed at identifying these foundational principles driving biological systems of plants, microbes, and multispecies communities relevant to DOE missions in energy and the environment.
Genomic Science program research is conducted at national laboratories and universities and includes single-investigator projects, multi-institutional collaborations, and fundamental research centers. The genome sequences of organisms studied in these projects are provided largely by the DOE Joint Genome Institute (JGI), an important user facility and a world leader in generating sequences of microbes, microbial communities, plants, and other organisms.
Genomics and Metagenomics. Sequencing and analyzing DNA from individual organisms (genomics) or microbial communities in environmental samples (metagenomics) form the foundation of systems biology research. In addition to sequencing and annotating genomes, Genomic Science program research seeks to develop improved methods for rapidly identifying and characterizing functional and regulatory gene networks in microbes, microbial communities, and plants.
Analytical Omics. Transcriptomics, proteomics, and metabolomics—collectively described as omics analyses—identify and measure the abundance and fluxes of key molecular species indicative of organismal or community activity. Global analyses of RNA transcripts, proteins, and metabolites inform scientists about organisms’ physiological status. Such analyses, as well as stable isotope tracking and nano secondary ion mass spectrometry (NanoSIMS) characterization techniques, also provide insights into gene function and indicate which genes are activated and translated into functional proteins as organisms and communities develop or respond to environmental cues. Metamethods that analyze DNA, RNA, and proteins extracted directly from environmental communities enable discovery of new biological processes and provide novel insights into relationships between the composition of communities and functional processes that they perform.
Molecular Imaging and Structural Analysis. Genomic Science program investigators are developing and using new methods for characterizing the chemical reaction surfaces, organization, and structural components in molecular complexes and tracking molecules to view cellular processes as they are occurring. Depending on the spatial scale, a variety of imaging technologies can be used to visualize the complex molecular choreography within biological systems. Some of these structural and imaging tools (e.g., synchrotrons, neutron sources, and electron microscopes) are available or are being developed at DOE Office of Science national user facilities. These facilities provide photon, neutron, electron, magnetic, and mechanical instrumentation with state-of-the-art spatial, temporal, and chemical sensitivity.
Predictive Modeling. Computational models are used to capture, integrate, and represent current knowledge of biology at various scales. For example, researchers are using genome sequence and other comprehensive datasets (molecular, spatial, and temporal data) to build models of signaling networks, gene regulatory circuits, and metabolic pathways.
Genome-Scale Engineering. Growing interest in biological design research stems from its wide-ranging potential. Knowledge of the principles that govern biology will enable predictions of biological system behavior under changing conditions. Moreover, tailoring the behavior of these systems for defined purposes will necessitate their reengineering or the design of new systems. Novel genome-scale engineering tools and technologies, in turn, will improve understanding of natural systems and their response to changing environmental conditions.