July 2010

A Look at the PSI Biology Initiative


A special session at the 2010 ASBMB meeting in Anaheim looked at the new biology phase of the Protein Structure Initiative - a large scale effort to accelerate discovery in structural genomics. This article details some of the topics that were discussed at that meeting. (Titled "NIGMS Introduces New PSI:Biology Initiative" in print version.)



 PSI:Biology – generating novel structures leading to new knowledge of the secrets of life.

In a special session at the 2010 American Society for Biochemistry and Molecular Biology annual meeting, the National Institute of General Medical Sciences introduced its new Protein Structure Initiative:Biology phase. During this phase, highly organized networks of investigators can apply high-throughput structure determination to study a broad range of important biological and biomedical problems.

During the session, PSI Director Ward Smith (NIGMS) described the components of the PSI:Biology network and ongoing opportunities for investigators to apply to become part of the program. The network includes five main components: centers for high-throughput structure determination, centers for membrane protein structure determination, the PSI-Structural Biology Knowledgebase, the PSI-Material Repository and consortia for high-throughput structural biology partnerships.

The first four components will support the solution of structures, dissemination of information and the storage and sharing of clones and vectors generated by the PSI. The fifth component provides funding for research on important biological problems and aids collaboration with the structure determination centers. The first awards for these components will be made this summer.

Next, Helen Berman (Rutgers University) explained the features of the PSI-Nature Gateway Structural Biology Knowledgebase. The Knowledgebase contains information on targets selected by the PSI and the status of efforts to determine their structures (TargetDB), information on protocols applied to those targets (PepcDB), highlights of technology developments and other accomplishments of the PSI, links to tools for the annotation of protein structure and function and access to the latest models and capabilities to model protein structures (Model Portal). It also provides an opportunity for scientists who are not part of the PSI:Biology network to nominate targets for structure determination.

For more information

• Information about the PSI-Biology Program and these funding opportunities.

• The PSI-Nature Gateway Structural Biology Knowledgebase.

• To nominate targets for structure determination by the PSI centers.

• The PSI-Material Repository.

Joshua LaBaer (Arizona State University) then talked about the PSI-Material Repository, which is now maintained by DNASU. This resource collects, sequence verifies, stores and distributes clones and vectors developed by the PSI. Plasmids are available individually or in thematic collections (e.g., all members of a protein family or derived from a given species). Processes have been developed to accelerate material transfer agreements.

John Gerlt (University of Illinois) described his interaction with the current PSI large-scale centers as a model for the way PSI:Biology is expected to work. His team used bioinformatics analysis of genomes to identify targets of unknown function within large enzyme megafamilies. Next, a large-scale center solved the structures of many of these targets. Gerlt’s team then used a combination of in silico and in vitro methods to identify potential substrates for these enzymes.

And finally, Susan Taylor (University of California, San Diego) commented on how the PSI:Biology network could benefit many researchers working on diverse problems. Some of the areas mentioned in the funding announcements include families and complexes of proteins and metabolic pathways or cellular compartments or that may be important in specific disease states.

Thus, PSI:Biology provides resources to benefit researchers beyond simply determining structures.

Peter C. Preusch (preuschp@nigms.nih.gov) is chief of the biophysics branch in the division of cell biology and biophysics at the National Institute of General Medical Sciences.

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