Program Leader: Mary Helen Barcellos-Hoff

The Cancer Program addresses three major research areas: radiation carcinogenesis, the biology of breast cancer, and novel therapeutic strategies. Fundamental understanding of the mechanisms underlying radiation carcinogenesis, its dose dependence, and its tissue specificity are a focus for the Department of Energy, based on its mandate to understand the health consequences of energy production. Life Sciences Division scientists have developed several widely applied models of normal breast and breast cancer to better understand the events leading to cancer.

Program Leader: Priscilla Cooper

The DNA Repair Program integrates multi-disciplinary approaches including molecular, biochemical, cell biological, and structural studies to achieve mechanistic understanding of the molecular machines involved in maintaining the integrity of the genome. A related focus is the coordination of these DNA repair processes with other cellular events including transcription, replication, telomere maintenance, and cell cycle control, as well as their regulation in response to both intrinsic and environmental DNA damage including low dose ionizing radiation. A major goal is to understand the relationship of genetic defects in DNA repair to cancer predisposition as well as to developmental, neurological, and immunological abnormalities, and premature aging.

Program Leader: Gary Karpen

The Nuclear structure and function (NSF)Program is focused on understanding the molecules and mechanisms responsible for the functions of genes, chromosomes, and nuclei. Members of this program are studying the roles of DNA sequences, proteins, and chromatin structure on gene expression, chromosome segregation, and the organization of chromosomes and protein complexes in the nucleus. Members use the results of their basic research to develop tools for diagnosis and treatment of human diseases, especially cancer.

Program Leader: Mark Biggin

The Genomes: GTL Program is focused on system wide functional and structural genomic analyses of microbes relevant to the Department of Energy's mission. Microbes have many potential applications that could revolutionize bioremediation, energy production and carbon sequestration. The Program's long term goal is to learn how to manipulate microbial metabolism to increase their usefulness. Members of the Program are developing high throughput methods to purify, detect, and characterize at structural resolution protein complexes in bacteria under a range of environmental conditions. Other members are microbe hunters, seeking to find new organisms with new capabilities.

The Genomes: GTL Program is currently organizing a lab wide Genomics: GTL science forum in collaboration with funded GTL projects centered in Physical Biosciences and Earth Sciences. The forum will take place on June 24, 2004. For information, contact Mark Biggin.

Program Leader: Tom Budinger

The Medical imaging Program has as its goal the development of imaging methods to investigate major illnesses such as atherosclerosis, heart disease, mental illnesses and cancer. The non-invasive imaging technologies include innovative nuclear detectors and imaging instruments, methods of data acquisition and reconstruction, and radiopharmaceutical tracer chemistry for positron emission tomography (PET) and single photon tomography (SPECT). Goals are to perfect techniques which will allow studies of molecular activities peculiar to pathophysiology in human patients and to apply these methods to detection and treatment of diseases.

Program Leader: John Conboy

The Membrane and cytoskeletal biology Program focuses on the morphological and functional differentiation of erythroid progenitor cells from erythroblastic islands in the bone marrow microenvironment to circulating enucleated erythrocytes. A major theme is the role of alternative splicing in generating functionally diverse, tissue-specific isoforms of prototypical erythroid cytoskeletal proteins that are physiologically important in membrane and nuclear processes in nucleated nonerythroid cells.

Program Leader: Bill Jagust

The Neuroimaging Program is aimed at using the techniques of positron emission tomography (PET) and magnetic resonance imaging (MRI) to understand brain function in normal and diseased states. A key interest is in the changes associated with aging and dementia. PET provides the ability to measure changes in neurochemistry that accompany aging and may be responsible for loss of function with aging in such important areas as memory, problem solving, and motor ability. MRI permits measurement of changes in brain structure that include atrophy of brain systems that are also responsible for cognitive and motor functioning. By combining molecular techniques for the study of function with anatomic techniques for the study of brain structure we hope to gain insights into factors responsible for optimal brain health in aging and the factors that influence the development of cognitive and physical decline.

Program Leader: Joe Gray

The Quantitative systems biology Program takes a multidisciplinary, "systems" approach to cell biology and cancer. This entails development of integrated high throughput analytical, computational and biological tools to analyze and understand responses of complex biological systems to external and internal stimuli. Our current goals are to apply this approach to understand and predict individual responses of normal and malignant epithelial cells to exposure to cancer therapeutics and radiation.

Program Leader: Amy Kronenberg

The Program in radiation biology conducts basic and applied research on the biological and physical effects of ionizing radiations. This research is supported by grants from NIH, DOE, NASA and other sources, and includes studies with sparsely ionizing radiations (X-rays, gamma rays), neutrons, alpha particles and highly energetic heavy ions. A major emphasis of the physics research is the interaction and fragmentation of primary ions similar to those found in the galactic cosmic radiation and in solar particle events. Other studies support the development of accelerator facilities for medical applications.

Research on the biological effects of ionizing radiations emphasizes interactions of radiation with DNA and chromatin, genetic regulation of radiosensitivity, alterations in gene and protein expression, and the molecular bases of carcinogenesis (including apoptotic regulation, mechanisms of mutagenesis, induced genomic instability and bystander effects), cataractogenesis and CNS effects. Particular interests include elucidating the molecular mechanisms underlying biological responses to low doses of radiation and in establishing the biological bases for improved prediction of the effects of exposure to space radiation environments.

Program Leader: Ken Downing

The Structural biology Program uses both x-ray crystallography, small angle x-ray scattering and electron microscopy to study macromolecular complexes in isolation and in context. X-ray and electron crystallography have been used in solving structures such as the BC1 complex, a major component in energy conversion; structures of several enzymes involved in DNA repair; and tubulin, the main protein in microtubules.