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Genomes to Life: A DOE Systems Biology Program

Genomics and Its Impact on Science and Society: The Human Genome Project and Beyond

Exploring Microbial Genomes for Energy and the Environment
The remarkable successes of the Human Genome Project (HGP) and spin-offs revealing the details of hundreds of genomes provide the richest resource in the history of biology. The new Genomes to Life (GTL) program of the U.S. Department of Energy (DOE) builds on these successes by combining DNA sequence data with advanced technologies to explore the amazingly diverse natural capabilities of microbes—the invisible organisms that thrive in every known environment on earth. The ultimate goal is to understand and use their diverse functions to meet critical DOE mission challenges in energy security, global climate change, and toxic waste cleanup.

Why Microbes?
The ability of this planet to sustain life is largely dependent on microbes, most of which do not cause disease. Microbes are the foundation of the biosphere, controlling earth’s natural biogeochemical cycles and affecting the productivity of the soil, quality of water, and global climate. As one of the most exciting frontiers in biology today, microbial research is revealing the hidden architectures of life and the dynamic, life-sustaining processes they carry out on Earth. Although microbes are recognized masters at living in almost every environment and harvesting energy in almost any form, we know less than 1% of them. Their sophisticated biochemical capabilities can be used for transforming wastes and organic matter, cycling nutrients, and, as part of the photosynthetic process, converting sunlight into energy and storing CO2 from the atmosphere.

GTL Scientific Challenges
Although we now have the entire genome sequences for hundreds of microbes, we still have very little understanding of how the information in DNA creates, sustains, and reproduces living systems. Obtaining this knowledge, a critical first step in harnessing microbial functions, requires a comprehensive approach extending from individual cells to many cells functioning in communities. Such studies must encompass proteins, multimolecular assemblies (sometimes called “molecular machines”; see figure) of components that work together, the intricate labyrinth of pathways and networks in which they interact, and cells. The wealth of data to be collected must be assimilated, understood, and modeled on the scale and complexity of real living systems and processes.

Large-Scale Technologies and Advanced Computing
computingJust as DNA sequencing capability was completely inadequate at the beginning of the HGP, the quantity and complexity of data that must be collected and analyzed for systems biology research far exceed current capabilities and capacities. Dozens of advanced large-scale technologies and approaches must be developed, with mathematics and computing guiding the research questions and interpretation at every step. Computational tools must manage and integrate the data into mechanistic models that describe how cells work. These studies eventually will enable an integrated and predictive understanding of how living cells function and respond to environmental changes, opening the door to using microbial capabilities.

technologyTo meet these challenges, DOE has planned four major research facilities that will make the most advanced technologies and computing resources available to the broader life sciences research community. Allowing new avenues of inquiry, this unique set of facilities will fundamentally change the course of biological research and greatly accelerate the pace of discovery. The facilities will provide scientists with the enduring and comprehensive ability to understand and, ultimately, reap enormous benefit from the functioning of microbial systems (see Genomes to Life).

The online presentation of this publication is a special feature of the Human Genome Project Information Web site.

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