Fundamental Genomic Science research includes single-investigator projects, multi-institutional collaborations, and research centers at universities and national laboratories across the country.
Multiscale Explorations Achieving a predictive understanding of fundamental life processes requires investigations that span multiple levels, from the information encoded in individual plant and microbial genomes to the functioning of cells as communities in an ecosystem. Important to this challenge is understanding the complex interactions between each level of biological organization and the environment.
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.
Bioenergy. Development of innovative approaches for sustainable bioenergy production will be accelerated by systems biology-based understanding of both (1) nonfood plants that can serve as dedicated bioenergy feedstocks and (2) microbes that can break down plant cellulosic biomass (e.g., stems and leaves) and synthesize biofuels and bioproducts from the component cell wall monomers. In addition to funding single-investigator and team projects in this research area, the Genomic Science program supports four DOE Bioenergy Research Centers.
Biosystems Design. Research in this area continues to help advance the rapidly developing field of bioengineering, often referred to as synthetic biology. Cutting-edge genome-scale engineering tools are opening new avenues for systems biology research, enabling the design of tailored plants and microbes while advancing fundamental understanding of biological function and inspiring novel approaches for its manipulation on a large scale.
Carbon Cycling and Environmental Microbiology. Omics-driven tools of modern systems biology are used to analyze interactions among microbial communities, plants, and their surrounding environments. Understanding the relationships between molecular-scale functional biology and ecosystem-scale environmental processes illuminates the basic mechanisms that drive key processes such as biogeochemical cycling of metals and nutrients, carbon biosequestration, and greenhouse gas emissions in terrestrial ecosystems. As part of this research, new techniques are being developed to analyze key bioprocesses in field settings.
Computational Biology. The ever-increasing complexity and diversity of data emanating from research within the Genomic Science program requires computational approaches to integrate these datasets and simplify their analysis and interpretation. The DOE Systems Biology Knowledgebase (KBase.us) is developing hypothesis-generating analysis techniques and simulation capabilities on high-performance computing platforms to accelerate collaborative, reproducible systems biology science, paving the way for new knowledge generation. Current KBase capabilities include apps for genome assembly, annotation, comparative genomics, metabolic modeling, expression analysis, and more. Also supported are capabilities for tool development and integration by third parties.
Addressing extremely complex science questions that span all scales of biology, research supported by the Genomic Science program requires the collective expertise of scientists from many disciplines and the coordinated application of a wide range of technologies and experimental approaches, including genomics and metagenomics, analytical “omics,” molecular imaging and structural analysis, predictive modeling, and genome-scale engineering.
Genomics and Metagenomics. Sequencing and analyzing DNA from individual organisms (genomics) or microbial communities in environmental samples (metagenomics) form the foundation for systems biology research. The DOE Joint Genome Institute is an important scientific user facility that generates high-quality sequences and analysis techniques for diverse microbes, plants, and other organisms relevant to DOE energy and environmental missions.
Analytical Omics. Transcriptomics, proteomics, metabolomics, and other analyses—collectively described as “omics”—identify and measure the abundance and fluxes of key molecular species indicative of organism or community activity. Global analyses of important cellular components such as RNA transcripts, proteins, and metabolites inform scientists about organisms’ physiological status. This research, along with chemical and structural analytical technologies including stable isotope tracking and nano secondary ion mass spectrometry (NanoSIMS), also provides insights into gene function and indicates which genes are activated and translated into functional proteins as organisms and communities develop or respond to environmental cues. Methods that analyze DNA, RNA, proteins, and other molecules extracted directly from environmental communities enable discovery of new biological processes and provide novel insights into relationships between the composition of communities and the 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 tools (e.g., synchrotrons, neutron sources, and electron microscopes) are available at DOE Office of Science user facilities that provide state-of-the-art spatial, temporal, and chemical measurement sensitivity.
Predictive Modeling. Computational models are used to capture, integrate, and represent current knowledge of biology at various scales. Researchers are using genome sequences and molecular, spatial, and temporal data to build models of signaling networks, gene regulatory circuits, and metabolic pathways that can be iteratively tested and validated to refine system understanding.
Genome-Scale Engineering. Genomes and systems-level understanding are uncovering the principles that govern system behavior, enabling genome-scale redesign of organisms. This research approach may involve building entirely new microbes from a set of standard parts—genes, proteins, and metabolic pathways—or radically redesigning existing biological systems to enable capabilities that the systems would not possess naturally.