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An Assessment of the National Institute of Standards and Technology Chemical Science and Technology Laboratory: Fiscal Year 2007 Biochemical Science Division SUMMARY The CSTL and new division leadership are making an impressive start in revitalizing this important area where NIST is expected to have strong growth. The Biochemical Science Division (BSD) has a wide array of scientific activities ongoing in three groups: DNA Measurements, Biospectroscopy, and Cell and Tissue Measurements. Structural biology at the Center for Advanced Research in Biology (CARB) and microfluidics activities have been transformed into three groups to promote better interactions. Two extramural efforts also are taking place: a marine bioscience and health program with the HML in Charleston, South Carolina, and work with the NCI on nanoparticle toxicity (nanoparticle toxicity work is also going on in the ACD). The BSD has formulated a set of strategic goals tied to the BioVision for NIST. Referred to as “mapping onto the omics,” the overarching goal is to integrate the various activities of the division into the emerging fields of genomics, transcriptomics, proteomics, metabolomics, and cellomics. By focusing on how NIST can provide measurement science and standards to these disciplines, the division believes that it will be able to align itself effectively with key national priorities and optimize the impact of its expertise. Overall, the strategy is an excellent one and should serve as a solid template for assessing BSD’s progress over the next few years. ADDRESSING NATIONAL PRIORITIES BSD has refocused its priorities to reflect the strengths that NIST can bring to the biotechnology enterprise. Health care and environmental issues; understanding basic biological mechanisms and translating this information into useful technologies; and incorporating new metrologies and standards into its mission are top priorities for the division. Because the U.S. Measurement System (USMS) was an important national priority and a far-reaching effort led by NIST, BSD should link its research more extensively into the findings of that recently completed study. A recent interdisciplinary team has completed an analysis of program opportunities in bioscience (biomarkers and systems biology) to understand and realign CSTL’s bioscience priorities. The next step will be for BSD to get external input in order to make sure that its program choices will have maximal impact in the scientific community. The new strategic focus holds promise for significant progress in the next year. IMPACT AND INNOVATION BSD has a solid track record for high-impact, innovative research that seems to be highly fragmented. Its members have contributed to the development of a BioVision for NIST. The recent Program Opportunities Task Force has attempted to tie these excellent pieces together via a small set of overarching research objectives that would increase cross-fertilization and leverage to meet larger unmet measurement needs, ideally in conjunction with the findings of the USMS study. These goals might impact about 20 percent of the research agenda, still allowing for the majority of the portfolio to be
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An Assessment of the National Institute of Standards and Technology Chemical Science and Technology Laboratory: Fiscal Year 2007 composed of smaller-scale research investigations. However, in these areas, some degree of top-down objective setting could focus the contributions. Collaboration across entities exists but is mostly bottom-up and project-oriented. The new division leadership has all the right management and organizational skills to successfully drive this forward. In addition, the division operates with relatively small teams (two or three scientists). A greater impact could undoubtedly be achieved with fewer but larger teams focused on key problems. The overarching themes that have emerged from recent strategic analysis are standards and technology for biomarker discovery and use and measurements, standards, and technology for understanding complex biological systems. BSD hopes to align its groups under these themes in order to achieve a high impact. This effort should be rapidly implemented. There are a number of programs that are innovative, well-motivated, and an example of NIST’s unique mission and capabilities: The program on array scanner error and calibration across platforms represents good science that aligns with the mission of NIST. It represents a unique ability to understand and standardize measurement as new applications of arrays go beyond gene expression. This work should be extended, most notably to comparative genomic hybridization, copy number variation, and microRNA. The program on DNA damage and repair measurements demonstrates excellent research that has resulted from years of contribution addressing challenging problems; it is even more valuable today than was anticipated at the outset. The program on DNA forensics represents excellent and important research on fundamental questions important to application needs. The program on quantitative cell biology demonstrates an impressive approach to multiplexed cellular measurements and quantitative cell imaging. This work addresses important unmet needs and directions for cellular pharmacology and diagnostics. The program on spore reference methods consists of very important, relevant, and useful research for biodefense and related applications. The program on biothermodynamics demonstrates very impressive measurement capability and understanding of the fundamental science. Some of the BSD’s strong research programs may benefit from a shift in direction to increase their significance or improve their alignment with NIST’s mission: The x-ray structural work is challenging research, but its only focus seemed to be the discovery of new structures, which seems better suited to academia. It is unclear how NIST gained value from this work. The research in understanding cellulose to glucose leverages NIST’s strong biothermodynamics core competency, but it is unclear whether this research is best done at NIST. For example, perhaps the Department of Energy or the National Science Foundation might be better able to drive efforts to gain a mechanistic understanding.
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An Assessment of the National Institute of Standards and Technology Chemical Science and Technology Laboratory: Fiscal Year 2007 While the microfluidics technology work appeared to be strong, its integration with cell biology was weaker and could benefit from collaboration with a biologist. As a result the microfluidics cell efforts seemed to lack purpose and direction. Systems biology is a key direction for biosciences investment, and it is good that this program has been launched in the cell and tissue measurements group. This is a good example of an area where higher level goals could be set that would drive greater integration of efforts, especially across informatics/biocomputing and biology, which appeared not as tightly linked as they should be. In general, success criteria for programs would benefit from improved clarity. Basic research and directed research aimed at advancing the distinct charter and role of NIST seemed uncoupled and at times at odds. Directed research cannot, of course, occur without a fundamental understanding of the challenges and trade-offs in the underlying science, but the BSD would be well-served to explicitly link its more basic research investments to the potentially important measurement-related outcomes that are envisioned for its research. Senior leaders at CSTL could provide greater context and vision to both postdoctoral staff and more junior staff on how their basic research efforts will impact NIST’s mission in the long term—that is, the business value of the standards linked to their more basic efforts. In this sense, especially for the more basic work, it was not clear that success and its impact were well defined. A study that can be done with a government research grant at a university and that does not advance measurement science and technology should not be done at NIST. BSD’s dissemination of results and products follows traditional scientific lines with articles in peer-reviewed publications as the primary mode. BSD and CSTL should formulate and communicate a clear strategy for invention disclosure and patents to stimulate the commercialization by others of their technologies and products. They should consider active participation in such standards organizations as ASTM F04. BSD should reach out to the basic and applied biology communities, initiating workshops and conferences that publish their proceedings and building an industrial advisory board to assist in setting priorities. TECHNICAL MERIT The quality of the research staff and their commitment to executing and publishing cutting-edge research are impressive. The technical merit of most of the research programs was outstanding, and the journals in which its researchers publish are of high stature. Scientists in BSD average two papers per year in good journals, and many are internationally recognized for their research. It is clear that this generation of researchers upholds NIST’s outstanding reputation for rigor in metrology, understanding, and control. CSTL is taking a broad approach to where it can contribute to standards. It has gone well beyond traditional areas for standards (e.g., it bottles precise chemical solutions) and is looking for nontraditional opportunities to advance the biosciences, such as work in databases; ontologies; and multiplexed, multivariate computation.
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An Assessment of the National Institute of Standards and Technology Chemical Science and Technology Laboratory: Fiscal Year 2007 INFRASTRUCTURE BSD leadership has appropriately created a flatter organization that integrates two of the five existing units into three main groups. This integration of microfluidics and CARB activities into the BSD will create greater opportunities for synergy and cooperation across the program. Having fewer and larger organizations also reduces competition inside the organization and allows for more free-flowing sharing of resources to address higher level priorities. Facilities and equipment are excellent, especially at CARB, which is located at the University of Maryland and whose infrastructure appears to be directly linked to its facility investments. Given the physical separation of BSD and CARB, the former should pursue opportunities for cross-site engagement through additional efforts such as Internet seminars and meetings, minisabbaticals, and other cross-site research opportunities. There are currently 57 staff members and 40 guest scientists in BSD. Given the number of projects being pursued, the scientists are clearly stretched, and the low ratio of technical staff to Ph.D. scientists means that most senior scientists operate with minimal technical support. New program goals will probably necessitate additional staff if the division is to keep pace with the rapid expansion of the biochemical sciences in the United States and the world. CONCLUSIONS BSD is clearly undergoing considerable revitalization, both organizationally and strategically. The creation of a BioVision for NIST is an excellent idea. To ensure successful achievement of its goals, division leadership must strive to bring in young scientists who are trained at the relevant scientific interfaces; this is critical in light of the fast pace of advances in the field. BSD should also settle on a small set of projects within the disciplines of genomics, transcriptomics, proteomics, metabolomics, and cellomics. The selected projects will serve as the basis for future evaluation of BSD’s progress.
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