National Institute of
General Medical Sciences

At the September 2003 meeting of the National Advisory General Medical Sciences Council, Dr. John Norvell reported on progress of and planning for the Protein Structure Initiative (PSI).  This presentation was a follow-up to discussion of the PSI at the May 2003 Council meeting.  At the May meeting, Council members had requested data on the success of the PSI pilot research centers in determining structures and the impact of the PSI on the field of structural biology.  Dr. Norvell addressed these questions at the September meeting and presented information on the organization, target strategy, and technical achievements of the centers.  He also presented recent scientific results from the research centers and discussed the revised mission statement for the PSI. 

 

Dr. Norvell described details of the plans for the PSI-2 production phase, which is scheduled to begin in mid-2005.  The second phase of the PSI is a component of the NIH Structural Biology Roadmap Initiative. This phase is envisioned as an interacting network with three components.  Large-scale research centers will operate as high-throughput structural genomics pipelines for the protein production and structure determination that is necessary for this production phase.  Each of these research centers will be expected to solve 200 or more unique protein structures each year.  This goal seems achievable based on the progress demonstrated in the pilot phase in developing protocols and automation for high-throughput operation for many protein targets.  Targets will be chosen as representatives of sequence families and will provide optimal structural coverage of sequenced genes.  Target selection policy, project milestones, and quantitative goals will be finalized following discussion on this topic at a fall workshop and a subsequent meeting of the PSI Advisory Committee, a working group of the Council. 

 

On the other hand, targets from some classes of proteins and organisms are especially challenging.  Because of the great variety of protein targets that will be required and the numerous unsolved bottlenecks that must be overcome, there is a crucial need for the establishment of specialized research centers.  These will comprise the second component of the PSI production phase.  These smaller centers are needed for development of new methods, technology, approaches, and ideas for protein production and structure determinations for especially difficult proteins.   Thus these specialized research centers will focus on membrane proteins, proteins from higher eukaryote/human, and projects to address technology barriers to high-throughput operation. These centers will be supported by NIGMS and possibly other NIH institutes and centers.   

 

Other specialized centers will comprise the third component of the PSI.  These centers will determine protein structures from microorganisms, tissues, or organ systems related to specific diseases.  These centers will not be supported by NIGMS, but will participate in the overall PSI network and be supported by other NIH institutes and centers.  The participation of other NIH institutes and centers in this NIH-wide program has not yet been determined.

 

The PSI pilot phase is currently (FY03) supported with an annual budget of $65 million total costs.  The budget for the final year (FY04) is expected to be similar.  NIGMS anticipates that new activities for production phase (FY05) will cost an additional $10 million. 

 

The Council approved the concept clearance for the PSI production phase.  The Council members discussed the PSI program and expressed satisfaction with current progress and the plans for the next phase.  Questions focused on ways to maximize the scientific and technical benefits of the PSI to the broad scientific community.  Dr Norvell was asked to develop these plans further and present them at the January 2004 Council meeting.  Copies of the slides for the presentation at the September 2003 Council meeting are posted in PowerPoint and accessible HTML formats.