BER Research Highlights

Search Date: May 25, 2017

12 Records match the search term(s):


December 04, 2006

DOE-Funded Scientist Named 2006 Scientist of the Year.

Jay Keasling of Lawrence Berkeley National Laboratory has been named 2006 Scientist of the Year by Discover magazine for his contributions to synthetic biology and its use to integrate genes from different species into a microbe to fabricate a drug for malaria. Keasling engineered yeast to produce artemisinic acid, a highly effective antimalarial drug that is normally extracted from sweet wormwood in a slow and expensive process. This work has resulted in a $43 million award from the Bill and Melinda Gates Foundation. Keasling is funded by DOE's Genomics:GTL program, not for his malarial research but for his fundamental research on how microbes respond to changes in their environment, information that will be important in developing biology based strategies for environmental remediation and bioenergy.

Contact: David Thomassen, SC-23, (301) 903-9817
Topic Areas:

Division: SC-23 BER
      (formerly SC-23 OBER)


November 20, 2006

The Sea Urchin Genome and its Regulatory Gene Networking

The DNA sequence of the purple sea urchin genome, with interpretations of gene function and their networking during embryogenesis is published in a special section of the November 10 Science magazine. The sea urchin is an ideal model system because it readily accepts DNA injected into the egg, and the effects can be observed using a simple light microscope. The overall genome analysis reveals a rich lode of information on gene function, evolution, and embryonic development. Among the more striking findings is that despite a much simpler body plan, the 23,000 genes sea urchin are only slightly fewer than the 26,000 genes of humans. Many of the sea urchin genes have representatives in humans, while there are many others evidently lost during the long evolutionary tract to the primates. With a capacity to digest tough sea kelp vegetation, some of the sea urchin digestive enzymes may also be of interest in broader biomass processing. This study was done in the Cal Tech laboratory of Eric Davidson, with a sub-contract to David McClay at Duke University. A schematic of the regulatory network is included on the large poster in the special section, with complementary audio-visual materials on-line at [website].

Contact: Marvin Stodolsky, SC-23.2, (301) 903-4475
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


November 19, 2006

ORNL Poplar Sequencing Team Receives Two Major Awards In One Night

Last week, Dr. Jerry Tuskan of ORNL, the head of the team that initiated and coordinated (with the DOE-Joint Genome Institute) the genome sequencing of Populus trichocarpa, the Black Cottonwood or poplar tree, received both the 2007 UT-Battelle Scientific Research Award and the ORNL Director's Award for Outstanding Team Accomplishment The awards were given "For scientific and technical leadership provided during a 5-year period leading up to the DOE-sponsored sequencing of the first tree genome, the assembly and annotation of that genome, and the publication of those results in Science." The fast-growing and widely dispersed poplar tree is a potential source of biomass for Bioenergy uses via the breaking down of the cellulose in its trunk into sugars and subsequent conversion to ethanol. Genome analyses will enable focused improvements in enzymatic deconstruction suitable for Bioenergy generation.

Contact: Dan Drell, SC-23.2, (301) 903-4742
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


August 07, 2006

Export of More Efficient Genome Sequencing Technology

The generation of DNA sequencing machines used in sequencing the human genome were fastidious, expensive, and fairly bulky. The Harvard Medical School lab of George Church pioneered a novel approach featuring much simpler instrumentation. The cleverness resides in designs for the front end DNA treatment and extensive parallelism of analysis. For commercial development , the technology has recently been purchased by the Applera Corp. An Applera subsidiary, Celera Genomics Inc., previously sequenced the human and mouse genomes in competition with public sector efforts. This commercialization promises easier export of the resources to other laboratories though the constituent steps are technically simple. The Church approach is one of several competitors for much cheaper and highly parallelized DNA sequencing technologies. These are applicable to either sequencing of single genes sampled across a large population, or to much cheaper sequencing of single genomes. For the DOE GTL Genomics Program, these approaches promise to drastically reduce DNA sequencing costs, both for new genomes and for verifying the sequence of useful recombinant constructs. One goal of these new approaches is to achieve re-sequencing of the human genome at a target cost of $1,000, at which genome sequence could become an affordable component of individualized medicine. A prize of at least $500,000 awaits the organization first achieving this goal, see [website]

Contact: Marvin Stodolsky, SC-23.2, (301) 903-4475
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


July 03, 2006

Structural Studies by LBNL Researcher Provides Insights into Regulation of Bacterial Gene Expression

Many microbes use two-component signal transduction as a method of information processing to control their adaptive behaviors in response to changes in the environment. The transmitter component receives the initial signal and modifies the receiver domain of the second component, called a response regulator; the signal pathway is then turned on or off by the status of the response regulator. Microbial nitrogen assimilation and metabolism is regulated by this type of two-component signal relay, with the NtrC response regulator controlling nitrogen scavenging pathways and nitrogen fixation. Featured on the cover of the June 1, 2006, issue of Genes and Development, LBNL investigator Professor Eva Nogales and colleagues report x-ray and electron microscopy structural biology studies of NtrC that provide new insights into the mechanism of regulation of bacterial transcription and gene expression. When activated by phosphorylation of its receiver domain, NtrC assembles into a donut-like hexameric ring that encloses and binds to regulatory promoter DNA sequences. The resulting conformational change in the molecular machine that produces mRNA, s54-RNA polymerase, thereby activates the entire polymerase machinery to initiate transcription of the required nitrogen assimilation genes, to produce a metabolic response to the original signal about the cells nutrient status. This new model suggests that conformational dynamics are crucial for understanding how a transcriptional activator interacts with RNA polymerase to regulate gene expression.

Reference: Sacha De Carlo, Baoyu Chen, Timothy R. Hoover, Elena Kondrashkina, Eva Nogales, and B. Tracy Nixon (2006) The Structural Basis for Regulated Assembly and Function of the Transcriptional Activator NtrC, Genes & Dev 20 (11):14851495.

Contact: Arthur Katz, SC-23.2, (301) 903-4932
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


June 26, 2006

Genome Sequencing of Unculturable Bacteria

Conventional DNA sequencing of a microbial genome usually entails extracting sufficient DNA from a culture grown up from a single bacterium; however, most microbes from natural environments do not have established laboratory culture conditions and, therefore, pose a challenge in providing enough DNA. This includes many strains of the most prevalent photosynthetic marine microbe, Prochlorococcus, which have major roles in carbon cycling and fixation. In the June 2006 issue of Nature Biotechnology, Dr. George Church led a GTL-funded team of MIT-Harvard Medical School scientists, in developing a new strategy that allows high-fidelity amplification of DNA from a single cell. The breakthrough comes from using DNA-digesting enzymes to cut away undesirable branched DNA structures that tend to form during early rounds of DNA amplification, leaving only linear DNAs to be tremendously amplified and subsequently sequenced. This technique allowed the genomic sequence to be obtained from a single Prochlorococcus microbe, and opens a window to obtain genomic information from individual members in complex microbial communities.

Reference: Kun Zhang, Adam C. Martiny, Nikos B. Reppas, Kerrie W. Barry, Joel Malek, Sallie W. Chisholm & George Church, (2006) Sequencing genomes from single cells by polymerase cloning, Nat. Biotech 24 (6): 680-686.

Contact: Marvin Stodolsky, SC-23.2, (301) 903-4475
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


June 12, 2006

An Integrated Model of Microbial Stress Response.

Lawrence Berkeley National Laboratory (LBNL) investigators Aindrila Mukhopadhyay, Adam Arkin, and Jay Keasling, together with co-investigators on the LBNL Virtual Institute of Microbial Stress and Survival (VIMSS) project, discover key clues to how the microbe Desulfovibrio vulgaris Hildenborough adapts its physiology to enable survival in habitats containing toxic and radioactive metal wastes and fluctuating hypersalinity. Using a variety of approaches such as transcriptomics, proteomics, metabolite assays, and electron microscopy, the VIMSS team applied a systems approach to explore the effects of a model stressor, excess NaCl, on D. vulgaris. They discovered that this microbe's coping mechanisms include importation of protective small molecules, the up-regulation of pump systems and the ATP synthesis (metabolic energy) pathway, changes in the stability of nucleic acids, changes in cell wall fluidity, and an increase in the activity of chemotaxis genes. The systems-level integration of data from multiple methods has led to a conceptual model for salt stress response in D. vulgaris that can now be compared to other microorganisms, leading to general, predictive models of microbial stress response and adaptation.

Reference: A. Mukhopadhyay, Z. He, E. Alm, A. Arkin, E. Baidoo, S. Borglin, W. Chen, T. Hazen, Q. He, H.-Y. Holman, K. Huang, R. Huang, D. Joyner, N. Katz, M. Keller, P. Oeller, A. Redding, J. Sun, J. Wall, J. Wei, Z.Yang, H.-C.Yen, J. Zhou, and J. Keasling (2006) Salt Stress in Desulfovibrio vulgaris Hildenborough: an Integrated Genomics Approach, J. Bact. 188 (11): 4068-4078.

Contact: Sharlene Weatherwax, SC-23.2, (301) 903-6165
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


April 03, 2006

BER Cancels Funding Opportunity Announcement (FOA) for Production and Characterization of Proteins and Molecular Tags and Plans to Issue New Solicitation for GTL Bioenergy Research Centers

The Department of Energy's Office of Science announced on March 28, 2006, that it is revising its plans for the deployment of new research facilities to support its Genomics:GTL program. As part of the reassessment, BER cancelled its FOA for a planned GTL Facility for the Production and Characterization of Proteins and Molecular Tags, issued in early January. The decision to reshape plans for the new GTL research facilities comes in response to the Presidents recently announced Advanced Energy Initiative and a review of the GTL program by the National Research Council (NRC) of the National Academies. The specific goal of the new plan will be to accelerate GTL systems biology research in the area of bioenergy, with the objective of developing cost-effective, biologically based renewable energy sources to reduce U.S. dependence on fossil fuels. The Office of Science plans to issue a new solicitation in the coming months for one or more centers for bioenergy research. Centers focused on systems biology research into carbon sequestration and bioremediation are also being considered for future years.

Contact: Marc Jones, SC-23.1, (301) 903-3072
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.1 Life Sciences Division, OBER)


April 03, 2006

DNA Diagnostic Chip Featured on Cover of Genome Technology Magazine

Featured on the cover of the March 2006 issue of the Genome Technology magazine is a DNA diagnostic chip used to display as color patterns, the numerous gene amplifications and deletions in cancerous tissues. The changes thus catalogued are a starting point for exploring devising possible cancer interventions. Each of the several thousand component pixels has DNA representing a short segment of the human genome. As a gene ordered array, the chip represents the human genome as its constituent chromosomes in overlapping segments of about 50,000 DNA subunits lengths. DOE sponsored resource and technology development contributed pivotally to this type of diagnostic capability. The DNAs are derived from Bacterial Artificial Chromosomes (BACs), with construction pioneered by the M. Simon team at Caltech. Under the now completed Human Genome Program, the prevalent resources for genome mapping and sequencing were the Caltech BAC libraries, with later complementation by libraries produced by the P. de Jong team now at the Oakland Children's Hospital. The genome scale DNA end sequencing with concomitant mapping of the BACs is related at [website]. It was critical to the strategies of the international public HGP collaboration and the private Celera Genomics Inc effort. The HGP was finished both within the projected time and budget. The strategy for displaying deleted or amplified sections of chromosome as simple color changes was pioneered by Joe Gray and Dan Pinkel, at UC San Francisco and the Lawrence Berkeley National Laboratory. These resources and capabilities together have fostered commercial production of several competing whole genome survey chips. The feature figure can be accessed through http://medphoto.wellcome.ac.uk as image B0005446.

Contact: Marvin Stodolsky, SC-23.1 (301) 903-4475
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.1 Life Sciences Division, OBER)


March 13, 2006

Office of Science Researcher Creates System that Visualizes the Production of Single Proteins in Live Cells

In the March 16, 2006, issue of the journal Nature, Professor Sunney Xie, Harvard University, describes a new imaging approach that allows the tracking of the production of individual proteins in a single living cell. The fluorescence-based technique will permit the study of the expression of many important proteins in the cell, including those produced in low numbers. In the Nature article, Dr. Xie was able to make quantitative measurements and observe protein production as a stochastic process, a series of discrete events recognizable as bursts of fluorescent molecules. This new technique improves upon standard techniques because it can visualize distinct biological steps while the standard approach is limited to measuring the combined average of these events. A unique aspect of this imaging technique isolates single cells in their own microfluidic compartments, thus improving the sensitivity of the fluorescent signal of each newly-synthesized protein. The research was supported by Genomics:GTL funding for the development of imaging techniques for the study of microbial molecular machines and cellular biology.

Contact: Arthur Katz, SC-23.2, (301) 903-4932
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


March 13, 2006

Office of Science Researcher on Cover of March 2006 Issue of Molecular Microbiology

Dr. Huilin Li, BNL, and his collaborators were featured on the cover of Molecular Microbiology for producing a series of structures of a protein destroying molecular machine called the proteosome. The proteosomes ability to rapidly degrade proteins is essential for the microbial cells ability to adjust to its environment by removing proteins that could interfere with the performance of newly produced molecular machines as well as disposing of cellular trash such as misfolded or inactive proteins or pieces. Dr. Li and his associates cryo- electron microscopy images reveal the cylindrical proteosome has closed ends, in contrast to x-ray crystallography data that had indicated an unstructured open form, and therefore poses new questions about how this machine works. The cryo-electron microscopy studies were supported by Genomics:GTL funding as part of research developing imaging techniques to be applied to the study of microbial molecular machines.

Contact: Arthur Katz, SC-23.2, (301) 903-4932
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.2 Medical Sciences Division, OBER)


January 16, 2006

Genomics:GTL Facility Financial Assistance Opportunity Announcement

The Funding Opportunity Announcement (FOA) for the Genomics:GTL Facility for the Production and Characterization of Proteins and Molecular Tags (i.e., GTL 1) was issued on Grants.Gov on Monday, January 9, 2006. The solicitation is open to all DOE/NNSA Federally Funded Research and Development Centers, as well as universities and not-for profit corporations. This FOA requests that the scientific community submit applications for the development of a scientific user facility for the Production and Characterization of Proteins and Molecular Tags that involves the design, construction (construction is used generically here and could include new construction, renovation of existing space, leasing space or other options proposed by the applicants), and research and development related to the design, configuration, and operation of the facility that will serve as a major scientific user facility for the scientific community including the Genomics:GTL program. Letters of Intent for the FOA are due on January 31, 2006. A conference call with potential applicants is scheduled for February 22, 2006, and all applications are due on April 11, 2006.

Contact: Marc Jones, SC-23.1, (301) 903-3072
Topic Areas:

Division: SC-23.2 Biological Systems Science Division, BER
      (formerly SC-23.1 Life Sciences Division, OBER)