Office of Biological and Environmental Research Weekly Report
January 18, 2001

Key Departmental News

Nucleosome Core Particle Structure Featured on Journal Cover. Researchers at the Oak Ridge National Laboratory (ORNL) have just reported a high-resolution structure of the nucleosome core particle (NCP). This work provides a foundation for further studies of the structure of the nucleosome itself, the structure of different DNA sequences, the effects of DNA damage on chromatin structure, molecular interactions that occur during genetic expression, and the biochemical basis of inherited diseases such as Rett Syndrome. The nucleosome is a complex of biological macromolecules that has a key role in DNA packaging and regulation of gene expression and DNA replication in the nucleus of cells. The structure is published in the December 2000 issue of Acta Crystallographica Section D (Biological Crystallography), the journal of the International Union of Crystallography, and is featured on the cover of the journal. The ORNL researchers first developed computational techniques to identify a specific DNA sequence that produced highly homogeneous reconstituted nucleosome core particles. The nucleosome core particles that resulted facilitated the growth of crystals that could diffract to high resolution. After preparation and purification of the complexes, crystals were grown in microgravity on a National Aeronautics and Space Administration (NASA) shuttle mission. The crystals were then analyzed by x-ray crystallography at the National Synchrotron Light Source at Brookhaven National Laboratory. Data were obtained that enabled construction of a structural model with resolution of 2.5 Å, allowing the positioning of more than 150 amino acids of the functionally important protein tails that were previously unobserved. The model shows how the NCP interacts with DNA and how this fundamental building block of the chromosome binds with dimethyl arsenate, an environmental toxin and potential carcinogen.
Contact: Roland Hirsch, SC-73, 3-9009

BER Researchers Selected for DOE Energy 100 Bright Light Award for a Biomechanical Pancreas. Researchers at Lawrence Livermore National Laboratory (LLNL) were the recent recipients of the prestigious DOE Energy 100 Bright Light Award for their research on the development of a Biomechanical Pancreas. An estimated 16 million Americans suffer from diabetes in the U.S. alone, where diabetes is the third leading cause of death by disease. Current methods of measuring blood glucose levels, often involving a finger stick, are painful, inconvenient, and prone to error. Additionally, it is virtually impossible to test frequently enough with current technologies to maintain relatively stable glucose levels. The biomechanical pancreas developed by Livermore, uses an innovative fluorescent chemical sensor to accurately monitor the glucose levels in the blood in real-time. The insulin pump is composed of a small battery-operated pump with an insulin reservoir and a computer chip that allows the user to control insulin delivery. The complete system is fully implantable in the body and thus, able to measure glucose levels continuously. This eliminates the need for diabetics to self-administer numerous daily insulin injections. LLNL has recently teamed with MiniMed, Inc., to further develop the chemical glucose sensor for biomechanical pancreas.
Contact: Dean Cole, SC-73, 3-3268