GTL Awards for FY 2006
Biotechnology and the microbial world hold the promise of solutions to
major Department of Energy challenges in energy, including the production
of ethanol and hydrogen, controlling the cycling of atmospheric carbon
dioxide
to minimize its impacts on global climate, and the cleanup of environmental
contaminants at former weapon sites. Unique microbial biochemistries amassed
over eons in every niche on the planet now offer a deep and virtually limitless
resource that can be applied to develop biology-based solutions to these
challenges.
At the heart of this effort is the Department’s Genomics:GTL (GTL)
research program whose goal is to use systems biology approaches to understand
microbes so well that their diverse capabilities can be harnessed for many
DOE and other national needs. DOE investments in genomics research over
the past 20 years now allow us to rapidly determine and interpret any
organism's complete DNA sequence.
Because it reveals the blueprint for life, genomics is the launching point
for an integrated and mechanistic systems understanding of biological function
and a link between biological research and biotechnology
solutions. With genomics data as a starting point, the GTL program is using
a systems biology approach to fundamentally transform the way scientists
conduct biological investigations and describe living systems.
A key GTL research challenge is to understand how microbes and communities
of microbes carry out their diverse and useful functions. We need to understand
living microbial systems, not just DNA sequences or proteins or cell by-products.
Thus, GTL is studying critical microbial properties and processes on three
systems levels – molecular, cellular, and community.
To further understanding of microbes and microbial systems at all three
levels, the GTL program is announcing six major research awards totaling
nearly $90 million over the next 5 years. These 6 projects involve
75 senior scientists at 21 different institutions – 4 national laboratories,
15 universities or research institutes, 1 federal laboratory, and 1 private
company.
Over the next 5 years, these new research projects will
-
provide understanding of microbial community function in
natural habitats and response to changes in their environments, information
that is essential for us to take advantage of the diverse capabilities
of microbes and microbial communities.
- develop new approaches for identifying and characterizing the proteins
being expressed within a complex microbial community.
- develop new strategies for looking inside microbes at the molecular
machines they use to carry out their diverse functions, for isolating
those machines, and for understanding their functions, capabilities that
are needed to use or modify microbial molecular machines to address DOE
mission needs.
- develop new computational tools that will allow scientists to better
organize, find, and use the complex and rapidly growing types and amounts
of information being generated in the GTL program.
The projects, lead institutions, and lead investigators are
-
Genome-Based Models to Optimize In Situ Bioremediation of Uranium and
Harvesting Electrical Energy from Waste Organic Matter. University of
Massachusetts, Amherst. Derek Lovley, Principal Investigator.
- Proteogenomic Approaches for the Molecular Characterization of Natural
Microbial Communities. University of California, Berkeley. Jillian Banfield,
Principal Investigator.
- Dynamic Spatial Organization of Multi-Protein Complexes Controlling
Microbial Polar Organization, Chromosome Replication, and Cytokinesis.
Stanford University. Harley McAdams, Principal Investigator.
-
High-Throughput Identification and Structural Characterization of Multiprotein
Complexes During Stress Response in Desulfovibrio vulgaris.
Lawrence Berkeley National Laboratory. Mark Biggin, Principal Investigator.
A high-throughput system to produce and characterize multiprotein
complexes central to the biological function of microbes
will be developed. This effort tests and integrates a production
system that utilizes microbiology techniques (production of tagged
proteins), new approaches for the isolation of complexes and
identification by mass spectrometry, imaging of multiprotein complexes
using electron microscopy, and the application of computational
analysis and modeling. The microbe Desulfovibrio vulgaris found
in metal and radionuclide sites is used as a model for understanding
how these complexes control a microorganism's ability to survive
in contaminated environments.
- Molecular Assemblies, Genes, and Genomics Integrated Efficiently. Lawrence
Berkeley National Laboratory. John Tainer, Principal Investigator.
A high-throughput system to produce and characterize multiprotein
complexes and modified proteins underlying microbial cell biology
will be developed. The project will produce an integrated
system that will test and develop technologies including high-throughput
advanced mass spectrometry and small angle x-ray scattering to
identify complexes and illuminate their physical configuration.
Computational approaches to information management
and the prediction of protein interaction and complex formation
will
be
integral. Microbes that live in extreme
conditions of high temperature will be exploited to expanded the
range of protein complexes and modified proteins that can be studied
by trapping unstable complexes in an environment of lower temperatures.
- An Integrated Knowledge Resource for the Shewanella Federation.
Oak Ridge National Laboratory. Edward Uberbacher, Principal Investigator.
This research will construct a data and knowledge integration
environment that will allow investigators from the Shewanella Federation
to query across the individual research domains, link to analysis
applications, visualize data in a cell systems context, and produce
new knowledge while minimizing the effort, time, and complexity
of
participating laboratories. The project will (1) Develop strategies
for capturing and integrating diverse data types into common data
models that support systems biology investigation, (2) Develop
tools and processes to catalog and retrieve high-throughput data
from
warehoused
and nonlocal data storage, (3) Construct a data and knowledge base
that integrates gene, protein, expression and pathway-level knowledge,
and (4) incorporate interfaces for navigation and visualization
of
the multidimensional data produced.
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