Development of Structural Neurobiology and Genomics Programs in the Neurogenetic Institute [report]

Brian E., M.D. Henderson
2006 unpublished
The purpose of the DOE equipment-only grant was to purchase instrumentation in support of structural biology and genomics core facilities in the Zilkha Neurogenetic Institute (ZNI). The ZNI, a new laboratory facility (125,000 GSF) and a center of excellence at the Keck School of Medicine of USC, was opened in 2003. The goal of the ZNI is to recruit upwards of 30 new faculty investigators engaged in interdisciplinary research programs that will add breadth and depth to existing school strengths
more » ... g school strengths in neuroscience, epidemiology and genetics. For the duration of the grant project period, and continuing to the present day, recruitment at the ZNI has been highly successful. Ten new neuroscience faculty have joined the ZNI since 2003, with an additional recruit joining the faculty by January 1, 2007. The ZNI will continue to search for quality faculty investigators over the next five year period, or until such time as the laboratory facility is fully occupied. A key component to the success of the ZNI recruitment efforts is the availability of myriad core laboratory facilities that support various faculty investigators' research programs. Two such core laboratories are the structural biology and genomics core facilities, and for which the DOE provided resources to purchase equipment. Structural Biology. The structural biology facility will house equipment necessary to determine three-dimensional structure of proteins and nucleic acid and will aid in understanding structure-function relationships. The structural biology group will focus on the elucidation of structural and molecular mechanisms in neurodegenerative diseases, and in particular, to attempt to uncover the molecular mechanisms by which protein deposits form in diseases such as Alzheimer's and Parkinson's. The DOE grant purchased the following equipment in support of the structural biology core facility: Bruker Biospin: Elexsys Spectrometer (partial) This new technology allows the analysis of spin labeled proteins using pulsed EPR spectroscopy. This technology allows significant improvements over the conventional continuous wave EPR spectroscopy. One of the main improvements is the ability to measure long-range distances using DEER or multi quantum coherence measurements. These methodologies extend the sensitivity from 25 Å (conventional continuous wave methodology) to 70 Å. One of the main drawbacks of distance measurements using conventional methods has been the fact that only close distances could be measured. Thus, it often required a good first guess to be able to place two probes in close proximity. Many experiments in which probes were not close enough have been uninformative. In addition, it has been very difficult to obtain long-range distance constraints to refine the structures of multi-domain proteins using conventional methods. Another significant new advance lies in the fact that multiple distances can be
doi:10.2172/894898 fatcat:3yjtlqu3pze2zbgpsevxtx7ire