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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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