Genomics:GTL

About the Program

About GTL

The Genomics:GTL (GTL) research program focuses on developing technologies to understand and use the diverse capabilities of plants and microbes for innovative solutions to DOE energy and environmental mission challenges.

The DNA code—the genome—for each living organism provides the blueprint for the biochemical processes of life. It is the platform for understanding the functionality of whole biological systems as they respond to and modify their environments. The genomes of individual organisms and systems of organisms (e.g., communities and ecosystems) contain the information and operating capabilities that determine structure and function across multiple scales of biological organization. At these scales, including spatial and temporal dimensions (see figure below, Multiscale Explorations for Systems Understanding), scientists investigate the functioning of individual proteins and other molecules. They also study molecular interactions, pathways, and vast interconnected networks within whole cells, communities, and ecosystems.

Microbes make up the foundation of the biosphere and sustain all life on earth. DOE has sponsored the genome sequencing of key model plants and hundreds of microbes relevant to generating clean energy, cleaning up toxic waste from nuclear weapons development, and cycling carbon from the atmosphere.

Building on sequenced genomes, the GTL program aims to use systems biology research to understand how genomes are translated into functional responses. Central to this approach is having the ability to measure and then model, in a coordinated way, the biological functions of a system and establish a mechanistic connection to its genome sequence. A complete computationally predictive, whole-system understanding of microbes and plants eventually will allow the design and engineering of biobased solutions to DOE missions.

The scientific understanding of a system attained in pursuit of one DOE mission will aid breakthroughs in other mission areas because of common underlying biological principles. This is the ultimate efficiency of the GTL program and of biology in general. GTL’s DOE mission focus and biological research approach have been affirmed by the National Academies of Science.

GTL systems biology research departs from traditional scientific methodology by addressing complex problems that require coordinated research among interdisciplinary teams from the life, physical, and computational sciences. To accomplish the desired in-depth understanding of biological systems in this new genomics-enabled era, an unprecedented integration of technologies, data and computing, theory, modeling, simulation, and experimentation must occur. Communication and research integration are even more important for GTL than for the HGP, which relied on only one dominant technology—DNA sequencing—and produced only one major dataset—DNA sequence. Myriad analytical technologies must be created, refined, and deployed to investigate and understand biological systems, linking different levels of biological discovery to gain a predictive understanding of whole systems—from cells to ecosystems.

GTL's mission is to provide sufficient scientific understanding of plants and microbes to develop robust new strategies to produce biofuels, clean up waste, or sequester carbon. This includes research that supports the development of computational models to direct the use and design of improved organisms carrying out these processes.

GTL’s ultimate scientific goal is to achieve a predictive, systems-level understanding of plants, microbes, and biological communities, via integration of fundamental science and technology development, to enable biological solutions to DOE mission challenges in energy, environment, and climate.

Derived from this goal are three objectives:

• Objective 1: Determine the genomic properties, molecular and regulatory mechanisms, and resulting functional potential of microbes, plants, and biological communities central to DOE missions. More…
• Objective 2: Develop the experimental capabilities and enabling technologies needed to achieve a genome-based, dynamic systems-level understanding of organism and community functions. More…
• Objective 3: Develop the knowledgebase, computational infrastructure, and modeling capabilities to advance the understanding, prediction, and manipulation of complex biological systems. More…

Multiscale Explorations of Life

Biology is a science of dynamic interacting systems, and no component of these systems operates in isolation. GTL researchers analyze key properties and processes on three fundamental levels.

• Molecular: Focusing on genes, proteins, multicomponent protein complexes, and other biomolecules that provide structure and perform the cell’s functions to understand how the genome determines dynamic biological structure and function at all scales, from genes to ecosystems, and to understand how proteins function individually or in interactions with other cellular components.
• Whole cell: Investigating dynamic molecular processes, networks, and subsystems controlled and coordinated to enable such complex cellular processes as growth and metabolism in cells.
• Microbial community and higher organisms: Exploring diverse cellular systems that interact to carry out coordinated complex processes that both respond to and alter their environments to determine how cells work in communities, tissues, and plants, and, ultimately, in global ecosystems.

The myriad biological structures and processes that exist within these three system levels are interconnected and coordinated by an intricate set of regulatory controls and continuous interactions with the environment. Exploring biology across all scales in a comprehensive and integrated way is essential to understanding how these systems operate in nature or in more application-oriented contexts related to new technology endpoints for DOE missions.

GTL Computing Environment

The GTL Knowledgebase will facilitate a new level of scientific inquiry by serving as a central component for the integration of modeling, simulation, experimentation, and bioinformatic approaches. The GKB also will be a primary resource for data sharing and information exchange among the GTL community. Furthermore, not only will the GKB allow scientists to expand, compute, and integrate data and information program wide, it will also drive two classes of work: experimental design and modeling and simulation. Integrating data derived from computational predictions and modeling, as envisioned in the knowledgebase project, will increase data completeness, fidelity, and accuracy. These advancements in turn will greatly improve modeling and simulation, leading to new experimentation, analyses, and mechanistic insight. Scientists’ ever-increasing exploitation of the dynamic linkages among data integration, experimentation, and modeling and simulation—aided by the GKB—will advance efforts to achieve a predictive understanding of the functions of biological systems. The knowledgebase, therefore, must serve multiple roles, including (1) a repository of data and results from high-throughput experiments; (2) a collection of tools to derive new insights through data synthesis, analysis, and comparison; (3) a framework to test scientific understanding; (4) a heuristic capability to improve the value and sophistication of further inquiry; and (5) a foundation for prediction, design, manipulation, and, ultimately, engineering of biological systems to meet national needs in bioenergy, environmental remediation, and carbon cycling.

Catalyzing Research and Industry

GTL will make data available to all scientists and industry, enabling cutting-edge investigations on the systems biology level and fostering participation by the greater community in solving DOE mission problems. This will facilitate rapid translation of science into new technologies and catalyze the industrial biotechnology sector of the economy.

Program Background

The GTL program began in 2002. Focusing on DOE mission goals, GTL’s approach in energy, carbon cycle, and environmental remediation involves (1) identifying research grand challenges through community input and workshops; (2) initiating proof-of-principle, high-risk pilot activities; (3) issuing solicitations for research strategies to build upon successful pilot projects; (4) establishing productive research partnerships; and (5) building a GTL Knowledgebase for integrating and sharing the biological information needed to solve these challenges.

GTL’s systems biology approach requires a wide range of capabilities and research styles. The GTL program includes participants from national laboratory science focus areas, academia (both individual researchers and members of teams), and industry. GTL employs DOE’s national user facilities [e.g., Joint Genome Institute (JGI) and Environmental Molecular Sciences Laboratory] and newly established Bioenergy Research Centers. The DOE Office of Biological and Environmental Research (OBER) partners with other organizations to help achieve GTL’s mission. GTL also uses resources and findings supported through programs at other federal agencies, sometimes collaborating via interagency solicitations.