Genomics:GTL

About the Program

2008 Strategic Planning Process

The GTL Strategic Plan will be available in mid-2008. Sharlene Weatherwax provided an overview of the strategic plan at the Genomics:GTL Awardee Workshop VI on February 11, 2008 and requested input from the research community. [PDF or PowerPoint]

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.

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 some 200 microbes relevant to generating clean energy, cleaning up toxic waste from nuclear weapons development, and cycling carbon from the atmosphere.

Before we can optimize or harness plants and microbial processes, however, they must be understood in far greater detail and in the realistic context of living, dynamic systems—whether as individual cells or communities of interacting cells—rather than as stretches of DNA sequence or isolated components such as single genes and proteins.

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

GTL analyzes key properties and processes on three 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.

Three Research Phases

GTL research is divided into three distinct phases. More...

• Transition from genomics to systems biology.
• Fundamental research technology integration and scaleup to address mission problems.
• Biological systems knowledge for DOE applications.

Achieving a Predictive Understanding Through Systems Biology

A comprehensive approach to understanding entire biological systems must encompass genes and proteins, multimolecular assemblies (“molecular machines”), pathways and interacting networks, whole cells, communities of cells, and environments. Surmounting the technical challenges presented by these multiscale explorations is a daunting prospect that will require dramatic improvements in research performance, throughput, quality, and cost. New capabilities also will be needed in computation, modeling, and simulation, which are integral parts of systems biology research.

Hence the GTL strategy rests on DOE's hallmark capabilities.

• Advanced technologies. GTL will scale up technologies in centers to address mission challenges by comprehensively analyzing the makeup and functions of living systems.
• Computing and information technologies. GTL will operate within an infrastructure containing data, tools, models, and communication resources for systems biology.
• Multidisciplinary teams focused on strategic science goals and managed for results. GTL will make its resources available to all scientists, enabling them to practice systems microbiology and thus involving the whole scientific community in important national problems. Proof-of-principle experiments in systems biology, technology prototyping, and piloting are in progress, and a community of scientists is becoming conversant with DOE mission challenges.

Research Centers, Integrated Computational Environment

Obtaining a predictive understanding of living systems requires analyses of great scale and complexity. To meet these challenges, technologies will be deployed and scaled up in research centers that will support the comprehensive level of analysis required for complete systems knowledge. An integrated computational environment will link all data with theory, modeling, simulation, and experimentation to derive principles and develop and test biosystem theories.

GTL Knowledgebase

Computational comparison of DNA sequences across species has become a powerful analytical technique, yielding insights into gene function and facilitating hypothesis development. In the new era of systems biology, all-against-all comparisons of the much more extensive data amassed in GTL—all linked to DNA sequence—will sharpen and accelerate insights into fundamental processes and research strategies. The GTL computational knowledgebase, along with high-throughput facilities, ultimately will reduce analysis time from many years to months, bringing more timely applications to national problems.

Catalyzing Research and Industry

GTL will make its resources, research centers, and knowledgebase 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. These enabling capabilities also will facilitate rapid translation of science into new technologies and catalyze the industrial biotechnology sector of the economy.

Program Background

The GTL program, begun in 2002, is in its initial phase, making the transition from genomics to systems biology. GTL-funded research projects collectively have set out to decipher, on a global scale, the molecular biochemistry and mechanisms for regulation of microbial and plant system processes.

The GTL program currently funds projects in academia, national laboratories, and the private sector. Contributions to the program are from experts in the life sciences, computing, mathematics, physics, chemistry, geology, oceanography, engineering, project management, and communications (see Research Progress).

GTL research projects are focusing on basic biological studies relating to mission-relevant systems. Scientists are conducting pioneering research, developing and using new generations of research technologies, learning how to apply computation and modeling, and working in multidisciplinary team environments. DOE BER has sequenced the genomes of nearly 200 microbes with wide-ranging biochemical capabilities. Some of the plants, microbes, and microbial communities being studied in GTL have potential for stabilizing toxic metals and radionuclides, degrading organic pollutants, producing energy feedstocks including biofuels and hydrogen, sequestering carbon, and playing a critical role in cycling ocean carbon and other elements.