National Institute of General Medical Sciences
National Institutes of Health
December 5-6, 2007
The PSI Steering Committee met late on the first day of the PSI annual meeting and continued on the morning of the second day. The Steering Committee consists of the fourteen PSI center directors, three members of the NIH staff, and five scientists not affiliated with the PSI. The work of the Steering Committee is performed by six subcommittees and the meeting began with brief summaries from the chairs of these subcommittees.
Subcommittee Reports
Goals and Milestones. Guy Montelione described the development of the Goals and Milestones document consistent with the overall PSI mission. These goals and milestones include metrics analyses that were presented to the PSI Assessment Panel and will be incorporated in the Knowledgebase. Additional metrics proposed by the subcommittee will also be presented in the Knowlegebase in the near future.
Target Selection. Andrzej Joachimiak summarized the efforts by the large-scale centers on target selection. The large-scale center directors and informatics co-directors have worked on this task on a daily basis, with workshops, weekly calls, etc.
Inter-Center Relationships. Tom Terwilliger described the conference calls for the directors and associates from specialized centers, modeling centers, and the materials repository. These calls serve an important function and represent an extension of subcommittee activities. There was a discussion of dissemination of technology developments to large-scale centers, but to be effective this needs participation from large-scale center representatives. There are other inter-center issues that go beyond specialized centers, including PSI-wide supplies of genomic DNA, PSI-wide coordinated promotion at meetings (KB might do much of this, but others could participate), PSI-wide coordinated recruitment of community targets and community functional studies. The steering committee could either reformulate the mandate or to have two committees.
Community Interactions. John Moult presented several specific suggestions (and elaborated on two of these later). These are excellent ideas, but most come at some cost and require organization. The Steering Committee needs to review these ideas and prioritize them.
Operations and Management Group (OMG). John Norvell described how this group of large-scale center directors and the PSI Network director plan for all aspects of operation of the large-scaled centers. Andrzej Joachimiak described activities focused on target selection, production goals, progress, metrics analyses, community outreach, and planned interactions with sequencing centers.
Bioinformatics Group (BIG). Adam Godzik presented an overview of the activities of the large-scale center bioinformatics staff on target selection and other informatics issues. BIG has coordinated the target selection and distribution for the four large-scale centers and played a crucial role in the first two years of PSI-2. Initial focus was on large families with no structural representatives, followed by consideration of very large families with few structural representatives and high biomedical interest (MEGA), possible coverage of model organisms, and recently inclusion of metagenomics families (META).
Discussion Topics
Most of the Steering Committee meeting time was devoted to selected topics of special current relevance to the PSI. Each of these topics was led off by short presentations to frame discussion that followed.
Metagenomics. Claire Fraser-Liggett gave an inspirational overview of human metagenomics. She described recent research in this field, initial results, and plans for further research. She also described new sequencing projects that are underway and opportunities for interactions and coordination between the metagenomics sequencing and biological centers and the PSI centers. Adam Godzik summarized the current PSI structural coverage efforts and the possible impact of a microbiome effort. There was considerable discussion on this issue.
Biology/Function. Ian Wilson presented the case that PSI now contributes to biology and functional characterization. He gave examples of progress on structural coverage and the value of the PSI structures. He also pointed out that the biological community does not know about this contribution and he asked how PSI might better address biology and function. Stephen Burley pointed out that the PSI infrastructure has now been developed and there are many worthy ways to use it to improve biomedical research. Strategic goals could include the microbiome, cancer, emerging diseases, environmental problems, etc. He also asked if the PSI centers should be permitted to work on functional experimental pursuits of their structures. The Steering Committee will find a means for further contemplation of these issues.
NIGMS Director Perspective. Jeremy Berg discussed possible projects beyond PSI-2. The Steering Committee asked to be consulted in such planning. The Steering Committee could be convened to meet in a timely manner in relation to NIGMS schedules, not just at our December annual meetings.
Challenging Proteins. Bob Stroud said that many aspects of membrane protein work can be “industrialized”, but the need for detergent-solubilization from membranes means that throughput is necessarily lower than for soluble proteins. Tom Terwilliger pointed out that it does not seem that methods are yet sufficiently mature for a productive high throughput approach to protein-protein complexes. Over all of PSI there have only been a handful of these structures. John Markley described why the production of eukaryotic proteins is substantially more difficult than for prokaryotic proteins, but structural analysis is not appreciably more difficult. Guy Montelione suggested that problems not taken up in large-scale center drafts because of perceived difficulty or ones proven not to work in subsequent efforts might be distributed to specialized centers. This is a complicated issue and it received a mixed response from the specialized centers.
Enhancing Community Relationships. John Moult suggested that the PSI has become too inward-looking, as a result of an understandable early focus on the technical challenges in meeting its 3000-structure PSI-2 goal. Much of the outside world is unaware of PSI, let alone the controversy about it. He urged the PSI to step up technology transfer and to attend meetings to get the word out. Ian Wilson and others cited a forthcoming Nature Methods paper and participation in past and future meetings. Clair Fraser-Liggett reinforced the need for promotion from her experience in infectious disease work. Most agreed that these activities should be centralized with the Knowledgebase. John Moult also argued that at this stage PSI target selection has become too disconnected from the biological community. He suggested that, starting immediately, PSI should choose some targets with community involvement and pursue more MEGA families and continue the emerging microbiome focus (META). Members agreed with these points, but several advised not to make large mid-course changes.
International Perspectives. Shigeyuki Yokoyama described the Japanese plans for a Structural Systems Biology project as a successor for the now completed Proteins 3000 project. He notes that elements of that plan, including molecular/cell biologists and chemical biologists together with structural biologists, may be relevant to PSI-3 thinking. David Stuart described the evolving scene in Europe with Framework 7 preparatory planning for core centers (cf. PSI large-scale centers) and associate centers (cf. PSI specialized centers). This requires buy-in from many countries for ultimate implementation. He also explored the need to move structure to center stage in biology and to integrate the full range of structural investigations from light and EM through to x-ray and NMR studies. He urged PSI to look for showcase examples of tech transfer (specialized centers to large-scale centers and PSI to the world), and he also cautioned that deviations from the current plan should be thought through very carefully so as to avoid criticism from such a change in direction.
Submitted by Wayne A. Hendrickson (Chair) on behalf of the PSI Steering Committee January 15, 2008
