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BIODEFENSE BRIEFING: Smallpox Grid Finished; NRC Holds Workshop on Access to Data; NIAID Funds BSLs, Issues Category A Progress Report

NEW YORK (GenomeWeb News), Oct. 3 - This week, the Washington, DC area buzzed with biodefense-related news and events.  At the British Embassy, participants in the Smallpox Research Grid feted the completion of the project,  while at the National Academy of Sciences, the National Research Council held a workshop to discuss issues surrounding access to genomic data for potential bioterror agents. And in nearby Bethesda, Md., the National Institute of Allergy and Infectious Diseases announced the recipients of over $180 million in funding to build national and regional biocontainment laboratories, and issued a 37-page progress report on its research agenda for CDC Category A agents.


Following are reports on these happenings.


SmallPox Research Grid Delivers Targets


Tuesday afternoon in a ceremony at the British Embassy, Todd Ramsey from IBM handed a DVD carrying data on potential smallpox drug leads to Army Brig. General Patricia Nilo.


The event officially marked the successful completion of the Smallpox Research Grid Project, a collaboration between teams at Accelrys, IBM, and United Devices, Oxford University and others to screen 35 million molecules as targets for blocking the topoisomerase protein in the smallpox virus-a key factor in the bug's virulence.


The project, which is the brainchild of Graham Richards, Oxford's chairman of chemistry and was funded in part by the United States Army Medical Research Institute of Infectious Diseases, harnessed the compute power of 2.5 million PCs volunteered by users in 195 countries, participants said. In total, the grid used 250,000 years of CPU time.


While this was not a genomics project per-se, it relied on genome data-in particular the recently sequence of smallpox, the 500-600 nucleotide sequence encoding the topoisomerase protein.


A challenge particular to this project was to ensure that the molecules selected would block the smallpox topoisomerase protein, but not the human topoisomerase, Graham said. When topoisomerase is hit with an effective compound, this inhibition prevents the virus' DNA from unraveling, and therefore inhibits the effectiveness of the virus, he explained.


Complicating matters is the fact that 9 separate models for topoisomerase exist. The best one of those along with the best 44 lead molecules were presented in the resulting data, which fits on some 30 or more DVDs of 4 gigabytes each.


For the project, the overall throughput of this grid actually exceeded everyone's expectations.  "This is so much computing power that most people who do this work can't get their heads around it," said Accelrys CSO Scott Kahn.


In fact, the grid represents the world's largest supercomputer right now, and is growing by 10,000 to 15,000 computers per week, according to Ramsey, who is IBM's general manager for global industry. "We think grid computing is only limited by our imaginations," he said. After all, there are 500 million personal computers in the world, and they are only using 10 percent of their available processing time, he noted.


Prior to the Smallpox Research Grid Project, this grid had been used in an Intel-sponsored project identify targets for 12 cancer proteins for Oxford University researchers, and in a Microsoft-sponsored project to find molecules that can block the assembly of the anthrax toxin for the US Department of Defense.


This Smallpox Research Grid project was coordinated by United Devices, an Austin, Texas-based distributed computing software vendor. United Devices distributed its software and Accelrys LigandFit software to participants in the grid. Next, the network was loaded with the target, topoisomerase, and the 35 million compounds were sent, 50 at a time, to the PCs on the grid for processing. The resulting data were collected at United Devices, and then FedExed to Accelrys in San Diego for analysis. The second stage of the project was to map the sequence of topisomerase onto the human structure.


IBM contributed a computing infrastructure based on eServer p690s and its DB2 database management software for the project. Additional participants included Evotec OAI, Robarts Research Institute, the University of Western Ontario, Memorial Sloan-Kettering Cancer Center, and Essex University.


Now that the data has been delivered, it is up to USAMRIID researchers to use the information gleaned from the research grid to develop a drug.


(Adrienne Burke, Genome Technology Editor-in-Chief, contributed reporting to this story.)


NRC Workshop Discusses Access issues to Bioterror Agent Genomes


A panel of scientists and security experts met Wednesday at the National Academies of Science for a workshop to discuss the issue of whether-and when-to allow open access to genomic data for potential agents of bioterror.


The workshop, organized by the National Research Council and attended by more than 40 people from academia, federal funding agencies, and government research labs, was intended as a basis for recommendations of a committee that will craft guidelines for sharing genomic information around sensitive organisms. For the full story on the workshop and what was discussed, see BioInform, 10-06-03 .


NIAID Funds National and Regional Biocontainment Labs


NIAID announced Sept. 30 that it was funding the construction of two National Biocontainment Laboratories with grants of $120 million each, as well as nine Regional Biocontainment Laboratories, with grants of between $7 million and $21 million each.


These awards will go toward building additional biosafety level 2, 3, and 4 lab space at the two NBLs, and BSL-2 and BSL-3 labs at the RBLs. These labs are designed for work on microbial pathogens that are of moderate health risk, (level 2), are serious or potentially lethal (level 3), and are lethal and aerosol-transmitted (level 4). They contain special engineering and design features such as double doors and seals that prevent the release of these agents into the environment, and protocols such as limited access and insect control.


The NBLs are closely tied in with the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases, eight centers to which the NIAID recently awarded $350 million in grants over the next five years. The RCEs will focus research on the US Centers for Disease Control's designated Category A pathogens, which include anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fevers such as ebola. The NBLs and RBLs are designed to give researchers the space to study these and other pathogens.


"There are very few places in the country where you can actually test new drugs and diagnostics on live pathogens that require containment at BSL level 3 or 4," David Gorenstein, professor of biological sciences and associate dean for research at UTMB School of Medicine, and a partner in UTMB's RCE proteomics core, told GenomeWeb News' sister publication ProteoMonitor in August.


While it had been thought that the NBLs would be located at RCEs, the NIAID spread out the grants somewhat, awarding the NBL and RBL grants to some institutions not involved in the RCE work: The two NBLS will be at one of the RCE's, the University of Texas Medical Branch at Galveston, and at Boston University Medical Center, which is not an RCE. Stanley Lemon will be the principal investigator at the UTMB NBL, and Mark Klempner, will be the PI at the Boston University NBL.


Other contenders for the NBLS were the University of Illinois Chicago, the University of California at Davis, and the Wadsworth Center in Albany, NY. All but the University of California Davis won grants as RCEs.


The nine RBLS will be at Colorado State University, Fort Collins, with Anthony Frank as the PI; Duke University School of Medicine (one of the RCEs), with R.S. Williams as the PI; Tulane University in New Orleans, with Paul Whelton as the PI; University of Alabama at Birmingham School of Medicine, with Richard Marchase as the PI; the University of Chicago/Argonne National Laboratory, with Thomas Rosenbaum as the PI; The University of Medicine and Dentistry of New Jersey, with Russell Joffe as the PI; The University of Missouri-Columbia College of Veterinary Medicine, with Joe Kornegay as the PI; the University of Pittsburgh, with Arthur Levine as the PI; and the University of Tennessee Health Science Center in Memphis, with Michael Dockter as the PI.


NIAID Progress Report Highlights Key Role of Genomics, Proteomics in Agency's Biodefense Efforts


In the last year, "tremendous progress has been made" in meeting the objectives set by a research agenda on Category A pathogens, the NIAID said in a report released Monday.


The progress particularly came in "the establishment of a research infrastructure," said the document, which is entitled "NIAID Biodefense Research Agenda for CDC Category A Agents Progress Report."


"In FY2002 and FY2003, NIAID developed more than 50 initiatives to stimulate biodefense research; approximately 75 % of these are new initiatives and 25 % are significant expansions of existing contracts," the report stated. "During this time, there was a 30% increase in the number of grant applications submitted and assigned to NIAID; the vast majority of these were in response to these biodefense initiatives."


This new spate of Category A work described in the report emerged from the recommendations set by a blue ribbon panel of outside experts on bioterrorism and its implications for biomedical research that met in February 2002, and was published in an initial report a year ago.


The Category A ramp-up includes 75 grant applications in the area of genomic/proteomic technologies for development of medical diagnostics, for which awards were to be made before the end of FY 2003 (which ended this week).


Included in the report are also updates on existing and new initiatives that the NIAID is planning under the biodefense program.


For example, in addition to the new extramural labs that the Institute is funding, NIAID said in the report that it will open a new intramural BSL-3 lab at Twinbrook in Rockville, Md., in January 2004.


It also promised that awards would be made soon (by the end of FY2003) under a new initiative, In Vitro and Animal models for Emerging Infectious Diseases and Biodefense, which will provide animal models for preclinical testing of new therapies and vaccines.


Meanwhile, it said awards are planned for FY 2004 under another new initiative, Identifying Targets for Therapeutic Interventions Using Proteomic Technologies, which is intended for development of new proteomic technologies designed for understanding pathogen and host cell proteomes, in order to facilitate identification of new targets, according to the report.


The NIAID has also "made a significant investment in the genome sequencing" of bioterror agents, according to the report. These include 14 completed strains of Bacillus anthracis and close relatives, by the Pathogen Functional Genomics Resource Center at the Institute for Genomic Research; a completed sequence of the Hall strain A strain of Clostridium botulinim, the complete sequence of Yersinia pestis, and near-complete or complete sequence of a least one strains of Franciseslla tularensis. 


For smallpox, the Poxvirus Bioinformatics Resource Center is doing sequencing and comparative genomics for different pox genes, having identified eight isolates of variola and three strains of vaccinia. Sequencing for related poxviruses including mosuepox, rabbitpox, camelpox, and monkeypox, are ongoing, and microarray-based approaches to viral genome sequencing are being developed in a collaboration with Affymetrix, the report said.


In FY 2004 ,the Institute plans to award grants under the Bioinformatics Resource Centers for Biodefense and Emerging Infectious Diseases, a new initiative that brings this genomic information into databases, .


To read the full progress report, click here.


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