Structural biology, the study of the shapes of biologically important molecules, is a foundational science in the understanding of life;it is principally the result of single crystal diffraction studies. The project """"""""Enabling Technologies for Macromolecular Crystallization"""""""" expands upon the work of the High Throughput Search Lab (HTSlab), a macromolecular crystallization facility at the Hauptman-Woodward Institute in Buffalo, NY. The HTSlab specializes in the development of high throughput methods to grow crystals of macromolecules suitable for diffraction studies;the formation of such crystals is a significant bottleneck in the science of structural biology. We will continue to partner with general biology, structural biology and structural genomics groups to undertake crystallization trials and enable analysis of these trials on as many as 1000 macromolecules each year. We will work in three areas: the provision of crystallization expertise and services for members of the three biology communities;the development and testing of crystallization methods and materials in a high throughput environment;and the integration of informatics services and tools for the analysis of crystallization results. We expect to work closely with the PSI community as it directs its further efforts toward a deeper understanding of the biology of complex systems.

Public Health Relevance

Structural biology studies the shapes of biologically important molecules, particularly macromolecules, to understand their function. Currently, 86% of all structures in the literature result from single crystal X-ray diffraction studies. Our work is aimed at helping researchers in the general biology, structural biology and structural genomics communities grow crystals for biomedically important projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM100494-04
Application #
8656135
Study Section
Special Emphasis Panel (ZRG1-BCMB-D (40))
Program Officer
Edmonds, Charles G
Project Start
2011-05-01
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
4
Fiscal Year
2014
Total Cost
$485,227
Indirect Cost
$235,110
Name
Hauptman-Woodward Medical Research Institute
Department
Type
DUNS #
074025479
City
Buffalo
State
NY
Country
United States
Zip Code
14203
Luft, Joseph R; Wolfley, Jennifer R; Franks, Eleanor Cook et al. (2015) The detection and subsequent volume optimization of biological nanocrystals. Struct Dyn 2:041710
Luft, Joseph R; Newman, Janet; Snell, Edward H (2014) Crystallization screening: the influence of history on current practice. Acta Crystallogr F Struct Biol Commun 70:835-53
Bruno, Andrew E; Ruby, Amanda M; Luft, Joseph R et al. (2014) Comparing chemistry to outcome: the development of a chemical distance metric, coupled with clustering and hierarchal visualization applied to macromolecular crystallography. PLoS One 9:e100782
Calero, Guillermo; Cohen, Aina E; Luft, Joseph R et al. (2014) Identifying, studying and making good use of macromolecular crystals. Acta Crystallogr F Struct Biol Commun 70:993-1008
Grant, Thomas D; Luft, Joseph R; Wolfley, Jennifer R et al. (2013) The structure of yeast glutaminyl-tRNA synthetase and modeling of its interaction with tRNA. J Mol Biol 425:2480-93
Luft, Joseph R; Snell, Edward H; Detitta, George T (2011) Lessons from high-throughput protein crystallization screening: 10 years of practical experience. Expert Opin Drug Discov 6:465-80
Luft, Joseph R; Wolfley, Jennifer R; Snell, Edward H (2011) What's in a drop? Correlating observations and outcomes to guide macromolecular crystallization experiments. Cryst Growth Des 11:651-663