Synchrotron radiation (SR) is an extremely bright and tunable x-ray source that enables forefront research in structural molecular biology (SMB). A ?Synchrotron Structural Biology Resource is proposed for continuing support at the Stanford Synchrotron Radiation Lightsource (SSRL) by the NIH NIGMS and DOE BER to develop new technologies in macromolecular crystallography, x-ray absorption/emission spectroscopy and small angle x-ray scattering/diffraction, to train/support users, and to disseminate the newly developed capabilities to the biomedical research community. This proposal is for the continued funding, operation and future development of this SMB Resource. New initiatives will capitalize on the increasing SR performance of SSRL?s 3rd generation storage ring SPEAR3. Proposed also is the development of selected SMB applications of LCLS. A principal aim is to optimize experimental facilities and instrumentation, detectors, software and compute performance on the SMB Resource?s 9+ beam lines at SSRL (with another two in construction) to take full advantage of the high brightness provided by SPEAR3 at 500 mA current and provide innovative new instrumentation and methodologies. This will enable the SMB Resource to advance the scientific forefront with new initiatives built upon state-of-the-art instrumentation and methodologies, innovative software and automated/high-throughput systems for: studying high resolution structures/function of large, complex biomolecules and molecular machines; investigating fundamental questions in biophysics such as protein folding; and developing/improving methods for studying very fast time-resolved structural changes in chemical and biological systems with ultrafast or fast scattering and spectroscopy techniques. These scientific advancements will be facilitated by parallel developments in software to provide expanded capabilities for instrument and detector control, remote data collection and real-time data analysis. Driving biomedical projects and collaborative research and service programs involving a large number of outside scientists will drive and support core technological developments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103393-38
Application #
9233142
Study Section
Special Emphasis Panel (ZRG1-BCMB-P)
Project Start
Project End
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
38
Fiscal Year
2017
Total Cost
$108,150
Indirect Cost
Name
Stanford University
Department
Type
Domestic Higher Education
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Yang, Yu; Liu, Fange; Liu, Aimin (2018) Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities. J Biol Chem 293:10415-10424
Sadler, Jessica B A; Wenzel, Dawn M; Williams, Lauren K et al. (2018) A cancer-associated polymorphism in ESCRT-III disrupts the abscission checkpoint and promotes genome instability. Proc Natl Acad Sci U S A 115:E8900-E8908
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Keable, Stephen M; Zadvornyy, Oleg A; Johnson, Lewis E et al. (2018) Structural characterization of the P1+ intermediate state of the P-cluster of nitrogenase. J Biol Chem 293:9629-9635
Dieck, Chelsea L; Tzoneva, Gannie; Forouhar, Farhad et al. (2018) Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia. Cancer Cell 34:136-147.e6
Vilbert, Avery C; Caranto, Jonathan D; Lancaster, Kyle M (2018) Influences of the heme-lysine crosslink in cytochrome P460 over redox catalysis and nitric oxide sensitivity. Chem Sci 9:368-379
Fransson, Thomas; Chatterjee, Ruchira; Fuller, Franklin D et al. (2018) X-ray Emission Spectroscopy as an in Situ Diagnostic Tool for X-ray Crystallography of Metalloproteins Using an X-ray Free-Electron Laser. Biochemistry 57:4629-4637
Bratkowski, Matthew; Yang, Xin; Liu, Xin (2018) An Evolutionarily Conserved Structural Platform for PRC2 Inhibition by a Class of Ezh2 Inhibitors. Sci Rep 8:9092
Glidden, Michael D; Aldabbagh, Khadijah; Phillips, Nelson B et al. (2018) An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein. J Biol Chem 293:47-68
Frank, Patrick; Benfatto, Maurizio; Qayyum, Munzarin (2018) [Cu(aq)]2+ is structurally plastic and the axially elongated octahedron goes missing. J Chem Phys 148:204302

Showing the most recent 10 out of 686 publications