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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
 Just 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.
 To 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).
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