Genomes to Life funds research in California
Two California-site Sandians are among the collaborators in newly announced DOE genomic research grants. Sandia/New Mexico leads another winning genomics proposal described last month (Lab News, July 26).
The awards are part of the department’s new "Genomes to Life" program that plans to take advantage of solutions that nature has already devised to help solve problems in energy production, environmental cleanup, and carbon cycling. Through biological, physical, and computational sciences, the program seeks to understand entire living organisms and their interactions with the environment.
"The fact that Sandia is participating in three of these laboratory awards validates and legitimizes Sandia’s emerging capabilities in biotechnology," says Deputy Director Len Napolitano (8130).
Sandia is a partner in the $36.6 million, five-year grant to Lawrence Berkeley National Laboratory to study "Rapid Deduction of Stress Response Pathways in Metal/Radionuclide-Reducing Bacteria." The team, including Anup Singh (8130), will develop computational models to describe and predict the behavior of gene regulatory networks in microbes in response to the environmental conditions found in waste sites contaminated with metals and radionuclides.
"Bacteria either convert the soluble, easily transportable metal compounds into insoluble compounds or immobilize them," Anup says. "Most of the sites are heavily contaminated so the bacteria need to survive in an environment that is very different from their natural environment."
To deduce how soil bacteria may aid site remediation, the team will compare types with varying levels of activity to see which cellular machinery (proteins and their assemblies, called complexes) is involved.
Sandia will focus on analyzing the proteins and protein complexes that act like molecular machines, Anup says, while most of the bioremediation-related microbial research will be done at LBNL. Other research partners are Oak Ridge National Laboratory; the University of California, Berkeley; the University of Missouri, Columbia; the University of Washington, Seattle; and Diversa Corp. in San Diego.
The individual microbes being studied under the grants have all had their genetic sequence determined through DOE’s Microbial Genome program (http://microbialcellproject.org/). Since it is the proteins that carry out almost all cellular functions, Sandia, LBNL, and Diversa will try to identify the relevant protein complexes in various bacteria, both "wild types" and mutant forms. When bacteria are exposed to stressful conditions, some alter their metabolism to ensure survival. Sandia will try to help identify and quantify proteins and complexes involved in bacterial stress-response pathways, examining large number of proteins at a time using its unique expertise and infrastructure in microseparations and mass spectrometry to determine the nature and composition of complexes.
LBNL will then use these data for computational models of how the genes controlling these pathways are turned on and off.
Identifying protein complexes
A second grant, to Oak Ridge National Laboratory for $23.3 million over three years, also targets proteins through a proposal entitled, "A Research Program for Indentification and Characterization of Protein Complexes." Malin Young (8130) brings to the collaboration a unique in-house capability, MS3D. This method to probe structure uses mass spectrometry to identify complexes embedded, like raisins in bread, in outer bacteria membranes. The complexes act as a "gatekeeper" for surrounding interactions. To gain structural clues, the complexes have been hooked chemically to their immediate spot in the membrane. This gives researchers a picture of how the assemblies nest there and function in their native state.
Other research partners are Pacific Northwest National Laboratory, Argonne National Laboratory, the University of North Carolina at Chapel Hill, and the University of Utah. The group will examine two microbes: Shewanella oenidensis, known for its ability to transform metals and toxic materials into harmless forms; and Rhodopseudomonos palustris, which absorbs carbon dioxide from the atmosphere and converts it into biomass.
"Success," Malin said, "will result in a knowledge base that can provide insight into the relationship between protein complexes and their biological function."