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From DNA Sequences to Living Systems ISSN: 1050–6101, Issue number 47 Vol. 11, Nos. 3–4, July 2001 In This Issue From DNA Sequences to Living Systems In the News Genomes to Life, Microbial Cell Project—Complementary New DOE Programs Explore Critical Life Processes Genomes to Life ........................1 OASCR and GTL.......................1 he complete DNA sequences for organisms ranging from humans to mice Tand microbes are presenting an even greater scientific challenge—to under- DOE Microbial Cell Project ........2 stand how life’s component parts function together and are influenced by envi- Human Genome Draft ...............3 ronmental factors in creating and operating dynamic living systems. DOE, a Genomes: A Perspective...........5 key player in the genomics revolution, is poised to make important contributions to this next grand scientific quest through the Microbial Cell Project (MCP) Honor for DeLisi ........................5 and the proposed Genomes to Life (GTL) program. New NIH Institute.......................6 Structural Genomics ..................7 The MCP takes a whole-genome development of appropriate tools. The approach to understanding the func- two programs will formulate more Synchrotron Use........................7 tion and regulation of all genes for a high-throughput methodologies for Proteome Organisation..............7 single living system and the pathways simultaneously studying many compo- Breast Cancer Research ...........8 in which the protein products interact. nents of living systems. The MCP will play a leading role in The extraordinary applications of this Nuclear Medicine.....................13 GTL, DOE’s major new undertaking. Toxicogenomics Center...........14 holistic approach will help DOE fulfill The GTL will build on previous Office its broad missions in energy, environ- Kettering Prize .........................14 of Science research that includes the mental remediation, and protection of Zeta Phi Beta Conference .......15 Human Genome Program and the human health. [For more details on Microbial Genomes..................18 Microbial Genome Program initiated GTL, see color centerfold and http:// in 1994. The plan for GTL is to use DOEGenomesToLife.org; for informa- Sloan-DOE Fellowships...........21 DNA sequences from both microbes tion on MCP, see article, p. 2, and à See color centerfold about GTL and higher organisms, including http://microbialcellproject.org.] between pages 12 and 13. humans, to systematically tackle ques- tions about essential life pro- Comparative Genomics cesses conserved across species. OASCR Joins OBER Sushi Delicacy ...........................8 Advanced technological and computational resources tested in Genomes to Life Program Arabidopsis Sequence...............9 and modeled in the MCP will he DOE Office of Biological and Envi- AAAS Prize................................9 be used to identify and under- Tronmental Research (OBER) and Office Microbial Conference.................9 stand the underlying mecha- of Advanced Scientific Computing Research nisms that enable organisms Mouse and Resources.......10–12 (OASCR) have formed a strategic alliance to to function in diverse environ- meet the challenges of studying complex sys- Resources mental conditions. tems. OASCR fosters and supports funda- Next-Generation Computing....17 In a sense, the MCP is advance mental research in advanced scientific HGMIS Resources...................19 reconnaissance for GTL, and computing and computational sci- ence—applied mathematics, computer sci- Other Resources ...............19–23 the two programs are and will remain closely entwined. ence, and networking—and operates For Your Information supercomputer, networking, and related facil- Both GTL and the MCP con- ities. These tools enable researchers to ana- Event, Training Calendars 22–23 tribute toward the shifting of lyze, model, simulate, and predict complex biology to a more quantitative phenomena relevant to DOE’s biological mis- Funding Information.................23 science, involving the collection, Subscription, Requests............24 sions. The proposed Genomes to Life program integration, and dissemination fits readily into this portfolio.à Acronyms.................................24 of diverse data and the All issues of Human Genome News are online (www.ornl.gov/hgmis/publicat/hgn/hgn.html). 2 Human Genome News 11(3–4) July 2001 In the News In addition to working with academic, DOE Microbial Cell Project nonprofit, and industrial partners, A Perspective by Daniel Drell DOE will take advantage of the sci- entific capabilities of its national ore than 50 scientists from such other disciplines laboratories. These capabilities Mcomplete as engineering; chemistry; physics; include high-throughput genomic microbial genome and the computer, imaging, and even DNA sequencing, microbial biochem- istry and array development and sequences have management sciences. been deciphered analyses; physiology; very high resolu- since the publica- Why Microbes? tion imaging; and structural biology. tion of the first in National user facilities such as 1995. These Microbes have evolved for 3.7 billion synchrotrons will play important sequences offer years and have colonized almost every roles, as will high-performance computing. scientists an Daniel Drell environment on earth. In the process, unprecedented DOE Human they have developed an astonishingly The MCP’s ultimate aim is to learn opportunity to Genome Program diverse collection of capabilities that enough about cellular functions so study cellular life in can be used to help DOE meet its chal- they can be manipulated knowledge- its simplest form lenges in toxic-waste cleanup, energy ably to enhance beneficial and sup- and to begin understanding how nature production, global climate change, and press unintended effects. MCP orchestrates the activities of living biotechnology. planners are well aware that it is systems. Additionally, their internal organiza- premature to explore manipulations This opportunity is at the root of DOE’s tion and complex regulatory systems or interventions. Given the complexity new Microbial Cell Project (MCP), allow microbial cells to adapt to a myr- of metabolic networks in even the begun in 2001 by the Office of Science’s iad of environments. They work as simplest cell, such actions would be offices of Biological and Environmental miniature chemistry laboratories, analogous to throwing the proverbial Research (OBER) and Basic Energy making unique products and carrying monkey wrench into a complex Sciences (OBES), allied with the Office out functions specific to their environ- machine; the outcomes most likely of Advanced Scientific Computing mental conditions. would not be useful and informative. Research (OASCR). OBER and OBES When greater knowledge is gained Understanding the complex function- contributed $12 million and OASCR about the parts, their interactions, ing of a single microbial cell ultimately $3 million through its Advanced the functional pathways to which will enable science to go far beyond Modeling and Simulation of Biological they belong, their partners in bio- just exploiting the beneficial capabilities Systems Program. chemistry, and their temporal and of microbes to meet DOE’s missions. spatial distribution within the cell, The challenges are great. Although the Much of the knowledge gained will these interventions—if and when complete list of life’s working parts for apply to cells in all living organisms. they merit exploratory research— sequenced genomes is now online, many The MCP thus represents a first step can be more precise and predictable. perform unknown functions. Addi- in moving from cataloguing molecular tionally, little is understood about how parts to constructing an integrative The MCP is as bold and major an and when the parts function together in view of life at the level of a whole undertaking as DOE’s Human living cells and respond to environmen- organism—microbe, plant, or animal. Genome Initiative was in 1987. tal changes. Gaining an understanding Much of the MCP’s research appeal of the complexities of systems-level Goals stems from the simple fact that this is where the science is leading. Like functioning also requires new ways of The MCP has four main goals: thinking and collaborations with fortunate children with their first Determine how microbial proteins Lego set who have seen the pictured combine into molecular machines item and know it can be built, we * Image Galleries that fulfill many of life’s important have opened the box and found the intracellular processes. pieces. The instructions are missing, High-quality, original graphics can be however, so we must complete the Characterize the internal cell environ- downloaded from the HGMIS Web site. construction through experimenta- ment and its effects on the proteins No permission is needed, but please let tion. Fortunately, we can build on HGMIS know where they were used. and protein machines that perform decades of intense biological Human Genome Project Information: functions relevant to DOE missions. research to make the job easier. www.ornl.gov/hgmis/graphics/ Characterize the intracellular dis- slides/images1.html tribution, quantities, and fluxes of The MCP makes its first grant awards Genomes to Life Program: the proteins and protein machines this summer. A list will be available via http://doegenomestolife.org/ inside a microbial cell. the Web (http://microbialcellproject. gallery/images1.html org/funding) and will be the subject Please cite the U.S. Department of Use high-end
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