Structural Genomics Centers included here fall into three categories:
Like many of the NIGMS-funded structural genomics centers, this one aims to
speed up structure determination by X-ray crystallography. It will focus 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
This Wisconsin-based center seeks to develop 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
This California-based center is developing high-throughput methods for protein
production, crystallization, and structure determination. It will initially
focus on novel structures from the roundworm Caenorhabditis elegans and
on human proteins thought to be involved in cell signaling. It will also determine
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
This consortium of seven institutions is working to reduce the average cost
of a protein structure from $100,000 to $20,000. The group will select 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
A collaboration of scientists in six countries formed to determine and analyze
the structures of about 400 proteins from Mycobacterium tuberculosis.
The group seeks to optimize the technical and managerial underpinnings of high-throughput
structure determination and will develop a database of structures and functions.
NIH's National Institute of Allergy and Infectious Diseases, which is co-funding
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
Five institutions in and around New York City and San Diego, Calif., will develop
techniques to streamline every step of structural genomics. The consortium expects
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
Researchers in New Jersey, New York, Connecticut, Washington State, and Ontario,
Canada will target proteins from various model organisms--including the fruit
fly, yeast, and the roundworm--and related human proteins. This consortium will
use 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
Researchers will analyze 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 emphasizes 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
This group aims 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
Active Sight provides access to the latest in crystallographic and protein engineering
technology to the drug industry.
President: Duncan McRee, Ph.D.
Location: 4045 Sorrento Valley Blvd., San Diego, CA 92121
[formerly Integrative Proteomics]. Affinium is a structure-guided drug
discovery company focused on the development of novel anti-infective medicines.
Chairman & CEO: John D. Mendlein, Ph.D.
Location: 100 University Avenue, 12th Floor (North Tower),
Toronto, Ontario CANADA, M5J 1V6
Plexxikon is a leader in the discovery and development of novel small
molecule pharmaceuticals to treat human disease.
CEO: K. Peter Hirth, Ph.D.
Location: 91 Bolivar Drive, Berkeley, CA 94710
Shamrock Structures determines the three dimensional structures of proteins
for biotechnology and pharmaceutical clients.
Location: 1440 Davey Road, Woodridge, IL 60517
Structural GenomiX (SGX) uses protein structures in the drug discovery process,
helping to create safer, more effective medicines.
CEO: Timothy J.R. Harris, Ph.D.
Location: 10505 Roselle Street, San Diego, CA 92121
Syrrx, Inc. is a drug discovery company committed to redefining the way medicines
are discovered.
President & CSO: Stephen Kaldor, Ph.D.
Location: 10410 Science Center Drive, San Diego, CA 92121
Vertex Pharmaceuticals is a global biotechnology company focused on the discovery,
development and commercialization of breakthrough drugs for a range of serious
diseases.
Chairman & CEO: Joshua Boger, Ph.D.
Locations: 130 Waverly Street, Cambridge, MA 02139; 11010 Torreyana
Road, San Diego, CA 92121;
88 Milton Park, Abingdon, Oxfordshire OX14 4RY U.K.;
Structural genomics group that specializes in high throughput structure determination
on a genome-wide scale.
BNL is independently taking a structural genomics approach to gain structural
information about human proteins that are involved in sensing and repairing
DNA damage.
The Genome Institute of Singapore seeks the integration of technology and biology
and will be facilitated by pursuing experiments of opportunity addressing questions
of high impact.
The Genome Science Centre in Canada has a primary mandate to deploy resources
and technology of a high-throughput genome mapping and DNA sequencing lab to
decrypt the genetic code, specifically to advance cancer research, diagnosis
and treatment.
The New Jersey Initiative in Structural Genomics and Bioinformatics (NJISGB),
sponsored by the New Jersey Commission on Science and Technology (NJCST), is
a pilot project aimed at developing technologies for high-throughput macromolecular
structure determination and their application in analyzing the massive stream
of data flowing from the Human Genome Project (HGP).
A consortium of several groups in the North West of England etablished a structure
genomics centre (NWSGC) to exploit the unique resources offered by their close
proximity to the UK´s current synchrotron radiation source (SRS) which
has already contributed to UK´s leading position in Structural Biology
-- they are the first structural genomics effort in the UK.
PRESAGE is a collaborative resource for structural genomics. It provides a database
of proteins, each of which has a collection of annotations reflecting current
experimental status, structural assignments models, and suggestions.
The PDB is the single worldwide repository for the processing and distribution
of 3-D biological macromolecular structure data.
The term "Protein Structure Factory" was chosen to represent a common
initiative of the German Human Genome Project (DHGP) and structural biologists
from the Berlin area aimed at the broad-scale analysis of proteins. The Protein
Structure Factory is established to characterize proteins encoded by the genes
or cDNAs available at the Berlin Resource Center of DHGP.
The Structural Genomics Project aims at determination of the 3D structure of
all proteins. This aim can be achieved in four steps : (1) Organize known protein
sequences into families. (2) Select family representatives as targets. (3) Solve
the 3D structure of targets by X-ray crystallography or NMR spectroscopy. (4)
Build models for other proteins by homology to solved 3D structures.
TargetDB is a target registration database that was originally developed to
provide registration and tracking information for NIH P50 structural genomics
centers. TargetDB has now been expanded to include target data from worldwide
structural genomics and proteomics projects. The scope of TargetDB is to provide
timely status and tracking information on the progress of the production and
solution of structures.
The Genomic Sciences Center at RIKEN, one of the foremost research facilities
in Japan, is dedicated to using the most advanced scientific facilities and
techniques to pursue systematic and broad-based research into the structures,
functions, and behaviors of the basic building blocks of life--genomes (gDNA),
genes (cDNA), proteins, gene cascades, protein networks, and plant and animal
models.
Structural Proteomics In Europe (SPINE) is an integrated research project which
brings together some of the top European structural biology institutions in
an unprecedented collaborative effort to develop new methods and technologies
for high-throughput structural biology.
Structure 2 Function (S2F) is a structural genomics projects that aims to solve
structures of these poorly characterized proteins by using X-ray crystallography
and protein NMR techniques. The initial set of targets was selected from the
first completly sequenced bacterial genome of the Haemophilus influenzae.
last updated December 18, 2003 - send corrections and comments to Angela Walker (alwalker@scripps.edu)
