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LBNL Human Genome Laboratory PUB-778 PROGRAM DIRECTOR'S REPORT FOR THE OFFICE OF Health & Environmental Research August 1996 I I / ( \ I I --- [ ') ( / /' / I ( I U'l & S'. '"0 tr (") c ., o CP Ill "0 I ., '< :j '< 1-' CD DISCLAIMER This document was prepared as an account of work sponsored by the United States Government. While this document is believed to contain correct information, neither the United States Government nor any agency thereof, nor the Regents of the University of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or the Regents of the University of California. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof or the Regents of the University of California. Program Director's Report for the Office of Health and Environmental Research August 1996 Prepared for Office of Health and Environmental Research Office of Energy Research U.S. Department of Energy Prepared by Ernest Orlando Lawrence Berkeley National Laboratory Berkeley, California 94720 operated by University of California for U.S. Department of Energy under Contract No. DE-AC03-76SF00098 PUB-778 ii iii Contents 1.0 OHER Program Summary 1.1 Director's Overview ................................................ 1 Program Integration .................................................. 5 Center for Environmental Biotechnology ····~········· 6 2.0 Program Organization, Facilities, and Resources ... 9 2.1 Organization and Management of OHER Programs Figure 1:LBNL and Division Org, Charts .............. 9 2.2 Budget Information Table 1&2: Budget Data & Staff ............................ 12 Figure 2: Sponsoring Agencies Pie Chart.. .......... 12 2.3 Personnel OHER Investigator List .......................................... 13 ,2.4 Table 3: Facilities and Resources .......................... 15 Advanced Light Source .......................................... 15 Imaging Facilities ....., ............................................... 16 National Tritium Labeling Facility ........................ 16 Biomedical Isotope Facility .................................... 16 Resource for Molecular Cytogenetics ................... 17 Transgenic Resource ................................................ 17 Life Sciences Microscope Resource ....................... 17 Yeast Genetic Stock Center ..................................... 17 3.0 Research Management Practices .................. :............. 19 3.1 Advisory Committees and Program Reviews ..... 19 President's Council on the National Laboratories-, .................................................................................... 20 3.2 Institutional Program Development Funds .......... 22 Table 5: Summary of Major Discretionary Funding Investements (OHER-related LDRD) ................... 22 3.3 Compliance with Animal Welfare and Human ..... Subjects ..................................................................... 23 Waste Minimization and Pollution Prevention ... 23 Safety Committees .................................................. 23 4.0 Research in Progress & Major Accomplishments .. 25 Analytical Technology ................................................... 25 New Instrumentation & Detection Methods ....... 25 iv Health Effects .................................................................. 26 Contents (continued) Tumor Biology ......................................................... 26 Radiation Damage and Genetic Toxicology ........ 27 Stem Cell Biology .................................................... 28 General Life Sciences ..................................................... 28 Structural Biology-Proteins ................................. 28 Structural Biology-Nucleic Acids ....................... 29 Structural Biology-Uses of the ALS .................... 29 Modeling Human Pathology in Transgenic Mice30 Human Genome Center ......................................... 30 DNA Repair ............................................................. 30 Medical Applications ..................................................... 32 The Center for Functional Imaging ...................... 32 Imaging of Apolipoprotein E-Binding Receptors In Vivo ....................................................................... 32 Table 6: Significant Science and Technology ...................... Achievements ......................................................... 33 Table 7: Major Examples of Collaborative Research ...... 47 Table 8: Patents, Licenses, CRADAs (FY 95-96) ............. 49 Work for Others ...................................................... 51 Table 9: Summary of Work for Others ............................. 55 5.0 Program Orientation/Future Directions (FY97-99) 63 Analytical Technology ................................................... 63 Health Effects .................................................................. 65 General Life Sciences ..................................................... 67 Medical Applications ..................................................... 73 Table 10: Facility Construction and Modification ............ 74 Table 11: Major Equipment Requirements ........................ 75 6.0 Contemporary Issues .................................................... 78 7.0 Appendices ..................................................................... 82 7.1 Information Transfer ............................................... 82 7.2 Conferences. Workshops, & Training Programs . 92 7.3 Extramural Activities .............................................. 92 7.4 OHER-Supported Publications ........................... 102 7.5 Selected Research Highlights ............................... 114 v I am very grateful for the assistance I received in pre­ paring this document. In particular, I would like to Acknowledgments thank the following people for their extraordinary contributions: Huber Warner, Assistant Deputy Director; Adele Sylar; Kati Markowitz; Tony Linard; of Life Sciences Division... ... as well as all of the fine scientists and engineers at "Berkeley Lab" whose research provided the inspi­ ration for this document. David Gilbert-Editor (please call 510-486-6096 with your questions or comments, or contact me through the Internet at de gilbert@ lbl.gov) vi OvERVIEW • 1 Since its establishment, the Department of Energy's Office of Health and Environmental Research (OHER) 1. OHER Program Summary has had responsibility for conducting biological research to develop the knowledge needed to identify, under­ 1.1 Director's Overview: stand, and anticipate the long-term health consequences of energy use and development, including the potential health impacts ofradiation. The Health Effects Research Program has established the basis for understanding the health consequences of radiation for humans, devel­ oped radiation dosimetry methodology, characterized and evaluated the health impacts of fossil fuels, and developed and conducted research to determine the health impacts of inhaled toxicants. The results of this research have provided input for setting genetic stan­ dards for radiation and chemical exposure. During the ensuing years the Ernest Orlando Lawrence Berkeley National Laboratory ("Berkeley Lab" or "LBNL") has emerged as one of the premier Biosciences research venues in the national laboratory system. LBNL performs unclassified basic and applied research and develops technologies in support of OHER. OHER's mission is to explore and mitigate the long-term health and environmental consequences of energy use and to advance solutions to major medical challenges. The ability of the Laboratory to engage in this mission de­ pends upon the strength of its core competencies. In addition, there are several key capabilities that are cross­ cutting, or underlie, many of the core competencies. We refer to these as foundations in order to distinguish them from the core competencies. CoRE CoMPETENCIES Bioscience and Biotechnology: Structural biology; Ge­ nome research; Bioinstrumentation; Cell and molecular biology, Molecular cytogenetics; Medical imaging; Biol­ ogy of human diseases; Radiation biology and; Biomolecular design. 2 • PROGRAM DIRECTOR'S OVERVIEW STATEMENT Environmental Assessment and Remediation: Ad­ sertion devices for synchrotron radiation; Large-vol­ vanced instrumentation and methods for environmen­ ume semiconductor-detector technology; Laboratory tal characterization and monitoring; Human health and automation; Advanced CADI CAM facilities for large ecological risk assessment; Indoor air quality; Subsur­ systems; Facilities for materials processing and fabri­ face remediation of contaminants; Geologic isolation of cation. high-level nuclear waste; Actinide chemistry. Education of Future Scientists and Engineers: Under­ Advanced Detector Systems: Major detectors for high- graduate, graduate, postdoctoral, and faculty involve­ energy physics, nuclear science, and astrophysics; ment in scientific and engineering research through Scientific conception and project leadership; Ad­ close ties with the
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