Note: This is an archived page that is not updated.
The Protein Structure Initiative ended 7/1/2015.
NIGMS supported the following pilot research centers in its Protein Structure Initiative.
Berkeley Structural Genomics Center (BSGC)
Like many of the NIGMS-funded structural genomics centers, this one aimed to speed up structure determination by X-ray crystallography. It focused on two bacteria with extremely small genomes to study proteins essential for independent life. The bacteria, Mycoplasma genitalium and Mycoplasma pneumoniae, are closely related. The former contains the smallest genome of any free-living organism and infects the human genital and respiratory tracts. The latter causes a form of pneumonia.
Organizations: Lawrence Berkeley National Laboratory, University of North Carolina, Stanford University
Principal investigator: Sung-Hou Kim, Lawrence Berkeley National Laboratory
Targets: Minimal genomes -- M. genitalium, M. pneumoniae
Technology: Robotic cloning; miniexpression screening; crystallization screening; automatic crystal changing and centering robots; computational filtering methods for target selection
Web site: http://www.strgen.org/
Center for Eukaryotic Structural Genomics (CESG)
This Wisconsin-based center developed high-throughput methods for protein production, characterization and structure determination from Arabidopsis thaliana, a plant that is frequently used in laboratory research and that has many genes in common with humans and animals, including genes linked to disease.
Organizations: University of Wisconsin, Medical College of Wisconsin (Milwaukee), Tokyo Metropolitan University, Molecular Kinetics, Inc., Hebrew University, Ehime University, CellFree Sciences (Yokohama), European Bioinformatics Institute-Hinxton
Principal investigator: John L. Markley, University of Wisconsin, Madison
Targets: Arabidopsis thaliana
Technology: Comprehensive LIMS for structural genomics; maskless array gene chip to screen cDNA libraries for presence of target genes; predictions of protein disorder for target selection; cell-free protein production; stereo-array isotope labeling for NMR
Web site: http://www.uwstructuralgenomics.org/
The Joint Center for Structural Genomics (JCSG)
This California-based center developed high-throughput methods for protein production, crystallization and structure determination. It initially focused on novel structures from the roundworm Caenorhabditis elegans and on human proteins thought to be involved in cell signaling. It also determined the structures of similar proteins from other organisms to ensure the inclusion of the greatest number of different protein folds.
Organizations: The Scripps Research Institute, University of California at San Diego, Stanford University, Stanford Synchrotron Radiation Labs, Genomics Institute of the Novartis Research Foundation
Principal investigator: Ian Wilson, The Scripps Research Institute
Targets: Thermotoga maritima, mouse
Technology: Crystallome screen of T. Maritima proteome; beamline automation; data centric informatics platform; nanovolume crystallization
Web site: http://www.jcsg.org
The Midwest Center for Structural Genomics
This consortium of seven institutions worked to reduce the average cost of a protein structure from $100,000 to $20,000. The group selected protein targets from all three kingdoms of life ( Eukarya, Archaea and Bacteria), with an emphasis on previously unknown folds and on proteins from disease-causing organisms.
Organizations: Argonne National Laboratory, Northwestern University, Washington University School of Medicine, University College London, University of Texas Southwestern Medical Center, University of Toronto, University of Virginia
Principal investigator: Andrzej Joachimiak, Argonne National Laboratory
Targets: Microorganisms, especially pathogens
Technology: HTP target selection; automated gene cloning, protein expression and solubility evaluation; low cost and high density fermentation; automated purification, crystallization and structure determination; computational methods for fold analysis and function prediction; databases and LIMS
Web site: http://www.mcsg.anl.gov
New York-Structural GenomiX Research Center (NYSGXRC)
Five institutions in and around New York City and San Diego, Calif., developed techniques to streamline every step of structural genomics. The consortium expected to solve several hundred protein structures from humans and model organisms.
Organizations: Structural GenomiX, Inc., Albert Einstein College of Medicine, Brookhaven National Laboratory, Columbia University, Rockefeller University, University of California at San Francisco, Weill Medical College of Cornell
Principal investigator: Stephen K. Burley, Structural GenomiX, Inc., San Diego, Calif.
Targets: Disease related proteins from eukaryotes and bacteria
Technology: Auto inducing media; His6-Smt3 protein expression vector; automation in protein production; automation in protein crystallization; automation in structure determination
Web site: http://www.nysgrc.org
Northeast Structural Genomics Consortium (NESGC)
Researchers in New Jersey, New York, Connecticut, Washington State and Ontario, Canada, targeted proteins from various model organisms--including the fruit fly, yeast and the roundworm--and related human proteins. This consortium used both X-ray crystallography and NMR spectroscopy to determine protein structures.
Organizations: Rutgers University, Columbia University, Hauptman-Woodward Medical Research Institute, Ontario Cancer Institute, Pacific Northwest National Laboratory, State University of New York Buffalo, University of Toronto, Yale University, Weill Medical College of Cornell, Mt. Sinai School of Medicine
Principal investigator: Gaetano Montelione, Rutgers University
Targets: Model eukaryotes -- D. melanogaster, S. cerevisiae, C. elegans, mouse, human
Technology: Systemic bioinformatics on domain families; crystallization image analysis; NMR reduced dimensionality data collection; automated analysis of NMR structures
Web site: http://www.nesg.org
Southeast Collaboratory for Structural Genomics (SECSG)
Researchers analyzed part of the human genome and the entire genomes of two representative organisms--the roundworm Caenorhabditis elegans and its more primitive microbial ancestor, Pyrococcus furiosus. The group emphasized technology development, especially for automated crystallography and NMR techniques.
Organizations: University of Georgia, University of Alabama-Birmingham, University of Alabama-Huntsville, Harvard Medical School, Duke University, Georgia State University
Principal investigator: Bi-Cheng Wang, University of Georgia
Targets: P. furiosus, C. elegans, human
Technology: Direct crystallography; NMR direct determination of backbone structures; self-learning crystallization system
Structural Genomics of Pathogenic Protozoa (SGPP)
This group aimed to develop new ways to solve protein structures from organisms known as protozoans, many species of which cause deadly diseases such as sleeping sickness, malaria and Chagas' disease.
Organizations: University of Washington, Seattle Biomedical Research Institute, University of Rochester, Hauptman-Woodward Medical Research Institute, Lawrence Berkeley National Laboratory, Stanford University
Principal investigator: Wim G. J. Hol, University of Washington
Targets: Disease related proteins from Leishmania species, Trypanosoma species, Plasmodium falciparum
Technology: Computational domain parsing; high throughput protein-pair discovery; new robots for crystallization in capillaries
* co-funded by the National Institute of Allergy and Infectious Diseases
TB Structural Genomics Consortium (TBSGC)
A collaboration of scientists in six countries formed to determine and analyze the structures of about 400 proteins from Mycobacterium tuberculosis. The group sought to optimize the technical and managerial underpinnings of high-throughput structure determination and to develop a database of structures and functions. NIH's National Institute of Allergy and Infectious Diseases, which co-funded this project with NIGMS, anticipates that this information also will lead to the design of new and improved drugs and vaccines for tuberculosis.
Organizations: Los Alamos National Laboratory, Albert Einstein College of Medicine, Texas A&M University, University of California Los Angeles, University of California Berkeley, Lawrence Livermore National Laboratory
Principal investigator: Thomas Terwilliger, Los Alamos National Laboratory
Targets: Disease related proteins from M. tuberculosis
Technology: Engineering proteins for solubility with GFP reporter; automation of crystallography structure determination
* co-funded by the National Institute of Allergy and Infectious Diseases