Genomics:GTL

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.