Life Sciences Division 1997-98 Progress Report

Life Sciences Division
1997-98
Progress Report

Overview
Mission
Structure

Systems Biology

Technology Applications

Foreword

This is the first formal progress report issued by the ORNL Life Sciences Division. It covers the period from February 1997 through December 1998, which has been critical in the formation of our new division. The legacy of 50 years of excellence in biological research at ORNL has been an important driver for everyone in the division to do their part so that this new research division can realize the potential it has to make seminal contributions to the life sciences for years to come.

This reporting period is characterized by intense assessment and planning efforts. They included thorough scrutiny of our strengths and weaknesses, analyses of our situation with respect to comparative research organizations, and identification of major thrust areas leading to core research efforts that take advantage of our special facilities and expertise.

Our goal is to develop significant research and development (R&D) programs in selected important areas to which we can make significant contributions by combining our distinctive expertise and resources in the biological sciences with those in the physical, engineering, and computational sciences. Significant facilities in mouse genomics, mass spectrometry, neutron science, bioanalytical technologies, and high performance computing are critical to the success of our programs.

Research and development efforts in the division are organized in six sections. These cluster into two broad areas of R&D: systems biology and technology applications. The systems biology part of the division encompasses our core biological research programs. It includes the Mammalian Genetics and Development Section, the Biochemistry and Biophysics Section, and the Computational Biosciences Section. The technology applications part of the division encompasses the Assessment Technology Section, the Environmental Technology Section, and the Toxicology and Risk Analysis Section. These sections are the stewards of the division's core competencies. The common mission of the division is to advance science and technology to understand complex biological systems and their relationship with human health and the environment.

Major thrust areas in the division include functional genomics and proteomics, biomedical technology research, bioanalytical science and technology, computational biology and bioinformatics, toxicology and risk analysis, life cycle analysis, and environmental assessment and remediation. Core programs are in place in functional genomics and in computational biology/bioinformatics. We will build on these programs to develop a strong proteomics effort. Closely related to this thrust is a proposal for a new Center for Structural Molecular Biology (CSMB) that was developed during this reporting period and is undergoing review during the Summer of 1999. The proposed CSMB would be a user facility that would provide access to a new small angle neutron scattering station at the ORNL High Flux Isotope Reactor (HFIR), to the special biological mass spectrometry facility at the Laboratory, and to our computational biology resources. With increased support for biomedical engineering both at the National Institutes of Health (NIH) and at the Department of Energy Office of Biological and Environmental Research (DOE-OBER), our ongoing projects in this area are being positioned to establish another core research program in the division. Our alliance with the ORNL Instrumentation and Controls (I&C) Division, and record of accomplishments coming from this partnership contribute significantly to our competitiveness in biomedical engineering. In addition we have been forming a partnership with the Biomedical Engineering Department at Vanderbilt University. We are strengthening program development efforts in the toxicology and risk analysis, life cycle analysis, environmental assessment and remediation areas through the Technology Applications Program in the division.

This report describes many technical highlights produced by the researchers in our division. A number of our scientists were recognized by significant honors and awards. A few examples include the election into the National Academy of Sciences of Dr. Audrey Stevens in 1998. Biological research at ORNL has been recognized since 1957 by the election of six researchers to the National Academy of Sciences (Alexander Hollaender, 1957; William Arnold, 1962; William Russell, 1973; Richard Setlow, 1973; Liane Russell, 1986, Audrey Stevens, 1998). Dr. F. F. (Russ) Knapp, leader of our nuclear medicine program, achieved the rank of Corporate Fellow, the highest distinction for scientists at ORNL. John Miller, head of the Biochemistry and Biophysics Section, was elected Fellow of the American Association for the Advancement of Science. Richard Leggett was elected to the National Council on Radiation Protection and Measurements. Annetta Watson accepted an invitation to serve on the U.S. Army Science Board.

A few personnel changes had impact on programs in the division. Richard Woychik, who was instrumental in launching the ORNL functional genomics initiative, took a position at Case Western Reserve University in 1997, and moved from there to Parke-Davis Pharmaceutical in 1998. Monica Justice accepted an offer from Baylor College of Medicine in 1998. Lisa Stubbs left the Laboratory to join Lawrence Livermore National Laboratory. Eugene Rinchik accepted the leadership position for our mouse mutagenesis program and joined the division in 1998. Yun You moved from Jackson Lab to join our mouse genomics program. DOE funding for our fundamental and applied cryobiology effort was significantly reduced and some of it reoriented in scope and direction. As a result, Peter Mazur, Corporate Fellow, and founder and leader of the program retired from the Laboratory and established his research laboratory at the University of Tennessee. Similarly, DOE funding for the protein engineering group was terminated. Fred Hartman, Director of the former Biology Division, Corporate Fellow, and founder and leader of this program, retired from the Laboratory and established a research laboratory at The University of Tennessee (UT). Charmaine Foltz joined the Laboratory as Institutional Veterinarian. In the division, she heads the Laboratory Animal Resources Section, which operates the Mouse Genetics Research Facility, a DOE user facility with a current average daily occupancy of 70,000 mice. At the end of this reporting period, Michelle Buchanan, leader of the biological mass spectrometry laboratory in the Chemical and Analytical Sciences Division (CASD) joined our division as Associate Director with special focus on providing leadership to our functional genomics program and on building our core efforts in proteomics and structural biology.

During this reporting period, we initiated a number of partnerships that are becoming more and more important for the future of our research programs. The Joint Institute for Biological Sciences (JIBS) was established between ORNL and UT to promote and develop support for collaborative education and research in biological sciences. UT organizations involved in this effort include the Medical Complex, the College of Veterinary Medicine, and the Institute of Agriculture. Barry Berven, Associate Director of our division, was named acting director of JIBS in September 1998. Work is under way to develop a strategic plan outlining specific goals for R&D, staffing, facilities and equipment, and funding. As part of JIBS, the UT/ORNL Graduate Program for Biomedical Sciences has been restructured into the Graduate Program for Genome Science and Technology. This program has been realigned under Life Sciences at both UT and ORNL to have greater involvement and relevance to research initiatives and educational needs at both institutions.

An April 1998 conference, "Partnering for Functional Genomics Research," attracted representatives from 14 pharmaceutical and biotechnology companies. All participating companies expressed interest in further interactions, and several new projects are being discussed. The Merck Genome Research Institute initiated a research project through JIBS. Other follow-on activities are under way to establish collaborative efforts and to pursue the development of an R&D consortium involving several industry partners.

On December 3, 1998, ORNL signed a memorandum of cooperation with a number of medical institutions in Tennessee. Participants include the University of Tennessee (Knoxville and Memphis), Meharry Medical College, Vanderbilt University Medical Center, and St. Jude Children's Research Hospital. This partnership, called the Tennessee Mouse Genome Consortium, is designed to facilitate collaborations among the participating institutions, using the ORNL Mouse Genetics Research Facility (MGRF) as a resource and partner in the research programs under the consortium umbrella.

We have been investing considerable effort into moving research labs out of obsolete facilities at the Y-12 site to the main ORNL campus. At the end of this reporting period only some 60 employees remain at the Y-12 site. These are researchers and staff whose work is associated with the MGRF. Groundbreaking for a new $2.8-million laboratory building at the ORNL site is occurring as this report is being finalized. A $12-million construction line item project, the Laboratory for Comparative and Functional Genomics (LCFG), is being planned for fiscal year 2001. The LCFG will be a modern animal facility that will house our mouse colony, rederived from frozen sperm and embryos, in a specific pathogen-free environment. Upon completion of these two construction projects, we will be able to close down the life sciences complex at Y-12. The LCFG is the first item of a planned $38-million investment by DOE-OBER into a Center for Biological Sciences (CBS) at ORNL. The CBS is planned as a modular complex of buildings, equipment, and infrastructure that will house current and future research programs in the areas of functional genomics, structural biology, proteomics, and systems biology. It will provide the environment for the ORNL biological research program to make significant contributions to biology during the next decade and beyond, with a special focus on complex biological systems research. Development of the CBS will enhance the advantages gained from the program's recent restructuring to embrace not only the biological sciences but also allied disciplines in information science and computing, analytical methodologies, and chemistry.