Now that the Protein Structure Initiative (PSI) has established efficient pipelines for determining the three-dimensional shapes of proteins, it is creating new mechanisms for sharing the resources it has developed with the scientific community.
The 10-year PSI effort, which started in 2000 and is sponsored by the National Institutes of Health’s National Institute of General Medical Sciences, funded a materials repository in September. Next year, it will create an information hub where researchers can search for and submit structural information. Meanwhile, PSI scientists will continue to develop new methods and tools for protein structure studies that are being commercialized by industry for mainstream use.
Information about protein structures can reveal the roles that these molecules play in health and disease and may point the way to designing new medicines.
“The first five years of the PSI were devoted to developing methods, technologies, and pipelines to speed the structure production process and reduce its cost,” said NIGMS Director Jeremy M. Berg, Ph.D. “The products of these efforts have been available to the scientific community, but the new resources should dramatically enhance accessibility.”
The Harvard Institute of Proteomics, part of the Harvard Medical School in Boston, Mass., will operate the PSI-Materials Repository (PSI-MR). With $5.4 million in funding over five years and under the direction of Joshua LaBaer, M.D., Ph.D., the new PSI-MR will store and ship PSI-generated clones, which can be used to make specific proteins for studies on their structure and function. Researchers will be able to order clones for a minimal fee to cover processing, handling, and shipping. Until the online catalogue is available, scientists requesting clones should contact the PSI centers directly.
“Producing clones is an essential—and often time-consuming—step in the protein structure determination process,” said PSI Director John Norvell, Ph.D. “By centralizing the availability of these materials, we put valuable resources at researchers’ fingertips that can free up time to explore important scientific questions.”
To date, the PSI research centers have produced more than 100,000 clones. Norvell expects the current centers to produce a total of 20,000 clones annually.
In fall 2007, the PSI will establish a “Knowledgebase” that will serve as a headquarters for structural information generated by its centers. For every protein, scientists will be able to find the best available information about the structure and biological function. The Knowledgebase also will offer experimental details about each stage of the protein structure determination process, regardless of whether the structure was successfully determined. Information about current PSI proteins being solved will be listed. In addition to searching these details, scientists will be able to submit requests for protein structures they’d like the PSI to determine.
The PSI centers will continue to deposit all solved structures in the Protein Data Bank (www.pdb.org ), an international structural database. So far, the centers have generated more than 1,700 structures from both simple and complex organisms. The majority of these are novel, sharing little structural resemblance to others in the PDB.
As the four large-scale PSI centers concentrate on churning out structures, the six specialized centers will continue to develop methods and tools that lead to more efficient and successful determination of challenging protein structures, such as membrane proteins and large protein complexes.
Many of the technologies conceptualized during the first phase of the PSI have been commercialized and are already being used in labs both large and small.
Such advances include:
- The miniaturization of samples needed to grow, purify, and crystallize proteins;
- Robotic systems to handle samples and image crystals;
- Enhanced software to analyze structural data and create higher-resolution images;
- More accurate screening processes to detect crystals suitable for imaging; and
- Improved systems for making proteins from machines, instead of cells.
These developments have reduced the cost, time, and space needed to carry out structural studies, as well as improved the generation and analysis of quality data.
To arrange an interview with Jeremy M. Berg, Ph.D., or John Norvell, Ph.D., contact the NIGMS Office of Communications and Public Liaison at 301-496-7301.
More information about the PSI is available at http://www.nigms.nih.gov/Research/SpecificAreas/PSI.
NIGMS (http://www.nigms.nih.gov), supports basic biomedical research that is the foundation for advances in disease diagnosis, treatment, and prevention.
The National Institutes of Health (NIH)--The Nation's Medical Research Agency--includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.