December 13-14, 2011
The PSI:Biology program seeks to leverage the high-throughput technology developed during the 10 years of the Protein Structure Initiative (PSI) to solve a set of important and complex biological problems. This is being accomplished through extensive partnerships with experts in biological systems where sweeping structural analysis can have a major impact in answering highly significant and challenging questions in biology. One important goal of the PSI:Biology program is to make resources for high-throughput structure determination available to a larger community of scientists. Another is to build a community of expertise in which the whole will be greater than the sum of the parts.
The second annual meeting, in December 2011, has reinforced the impression that PSI:Biology is well on its way toward accomplishing its stated mission. The five main components (High-throughput Structure Determination (HTP) Centers, Centers for Membrane Protein Structure Determination, Consortia for High-throughput-enabled Structural Biology Partnerships, PSI Structural Biology Knowledgebase (SBKB), and Materials Repository) interface well and work towards the common goal of advancing biology through high-throughput structural biology.
The meeting provided an informative mix of 10- and 30-minute 'science talks' on the biological impact of the ongoing research. The oral presentations were selected by members of the Advisory Committee from the volunteered abstracts, and many of the speakers presented impressive accounts of the 'enabling power' of PSI biology. Several speakers mentioned that the partnerships affected, in a positive way, their approach to science, and this is exactly one of the stated goals of PSI:Biology. These talks were interspersed with combined progress reports from the HTP Centers, Membrane Centers and biology partners, and from committees addressing materials, outreach, goals and metrics, and target definition, respectively.
Below we briefly summarize key issues that were raised during the annual meeting and provide feedback that the Advisory Committee offers to help insure success of the program as it approaches mid-term review.
A. Centers and Partnerships - the Network
- The Centers for Membrane Protein Structure Determination and their partners have achieved an admirable level of cooperation and synergy. These centers are united by their own unique set of challenges that serves as a paradigm for PSI:Biology.
- The strong link among the four Centers for High-Throughput Structure Determination has contributed greatly to the success of PSI-1 and PSI-2. It was felt that the connection among the four HTP centers, which were previously united in their quest of methods development, has weakened somewhat, and the committee encourages the centers to strengthen communication for optimal synergies.
- Along those lines, many of the participants felt that a separate, smaller meeting or breakout session would be useful for sharing technologies and recent developments; this could also entail a discussion of 'road-blocks', and may be coupled with a business meeting regarding the SBKB and Materials Repository (see below).
- Initial difficulties in balancing the collaboration between HTP centers and their biology partners have largely been resolved. We suggest that the lessons learned from this 'adaptation phase' be made accessible to future PSI collaborators. This will be especially important if NIGMS moves towards an R01 supplement mechanism to bring in more biology collaborators (see below).
- The members of the Advisory Committee would appreciate a common format for the progress report. This would make evaluation of progress much easier.
- Members of the Advisory Committee will investigate individually the possibility of attending annual meet-ings held by the HTP centers and to utilize this time for a site visit.
B. PSI Structural Biology Knowledge Base and Materials Respository
- The SBKB has done an excellent job in curating structural information resulting from the ongoing efforts; the Web site has a plethora of information that should be useful to the scientific community at large. The SBKB is encouraged to conduct user studies to gather functional requirements and scientific use cases from the broad biology community to further improve the utility and usability of the Web site.
- The Materials Repository is to be applauded for its efforts to collect and curate PSI-related plasmids; it is well on its way of becoming a useful resource for the scientific community within and outside PSI:Biology.
- One particular challenge arises from the greatly increased heterogeneity in the types of information ac-quired by PSI:Biology compared to PSI-1 and PSI-2. In addition to depositions to the Protein Data Bank (PDB) and SBKB of targets, structures, homology models, publications, protocols and technologies, a large amount of raw experimental data is being collected. Materials such as plasmids and expression vectors are being collected by the Materials Repository. All of this is of great value to both the PSI:Biology partners as well as the community at large. However, its storage and curation present significant challenges.
- To address these challenges, we suggest that a 'business meeting' for all PIs be held after each annual PSI:Biology meeting where PIs and database curators can discuss issues and streamline submission and deposition pipelines to minimize administrative overhead from both sides. Particular challenges are presented by the requirement to capture collaborative efforts as well as to document the impact of PSI achievements and address whether the power of high-throughput structural biology has been leveraged.
- With the mid-term evaluation coming up, there is an urgency to decide what exactly should be captured by the SBKB. This information should be mandatory, and it is recommended that NIH staff regularly solicits compliance reports from the SBKB. However, it is recognized that the administrative overhead generated by database input should not get in the way of doing the research, and so all requirements have to be carefully balanced.
- With respect to the biology partnership, it should be clear at the outset as to which partner is submitting what type of information to the SBKB; the entire burden should not rest with the centers.
C. Outreach and Impact
- Members of PSI:Biology have published over 100 articles, several in high impact journals. We recommend that all published research and research presented at meetings clearly acknowledge PSI:Biology and includes references to the various repositories.
- PSI:Biology has reached out to the computational community, and this has had an impact on ongoing structure prediction efforts. The 'leveraging factor' resulting from computational prediction of structures could be included in metrics (see below).
- A number of difficult structures have been determined by the membrane protein centers.
- The SBKB and Materials Repository are well-represented at many meetings. These efforts have been not quite as successful at reaching the biologists, and this is an area of future improvements.
- Efforts to educate biologists about effective ways of visualizing and utilizing structural information are ongoing. For example, the PDB has a tutorial for beginners that is an excellent starting point, but perhaps awareness should be raised in reviews written specifically for biology journals.
- Members of PSI:Biology are actively involved in outreach at the undergraduate or high-school level. This should be encouraged and facilitated, perhaps by making teaching and outreach resources available to all members of PSI:Biology.
- PSI:Biology has continued to leverage major initiatives (such as the Human Microbiome Project and other NIH programs) and has broad international impact (such as networking with Russia and China). Such leveraging is strongly encouraged to harness the power of PSI:Biology.
- The discussion on 'metrics' is ongoing. With PSI:Biology tackling problems of increasing complexity, metrics like 'impact' or 'challenge level' (albeit more subjective) should be considered in addition to 'structure counting'. Leveraging and enabling power of PSI:Biology should also factor into metrics.
- Much of the information is already being captured by the SBKB; other information pertaining to biology and biological relevance needs better definition. Obviously, metrics that haven't been defined cannot easily be captured. It is suggested that a workshop be organized sooner rather than later to put definitions on paper.
- Ultimately, the committee feels that each group will have to finish the statement 'PSI:Biology is a success because….' in a meaningful manner.
D. Looking Forward Scientifically
- Progress in the past year has highlighted the power and transformative nature of PSI:Biology. To fully integrate structure into the biological sciences, information exchange must go both ways.
- Studies of multi-domain proteins and macromolecular complexes are increasingly moving to the forefront for HTP centers and many of their biology partners. The different centers are encouraged to share technology that could benefit this particular common goal.
- The HTP centers should continue to accept community nominated projects; however, the communicator's commitment must be ensured and maintained. This could perhaps be done through site visits or mini-sabbaticals at HTP centers by community nominators. The Advisory Committee would like a more compre-hensive report on the state of community-nominated projects.
- The Advisory Committee recommends spending the remaining funds originally allocated for U01 announcements for supplements to R01s, which can be reviewed by staff. It is important to reduce the 'acclimatization phase' between the two partners to a minimum; lessons learned from previous experiences could be of help here.
From the PSI:Biology Advisory Committee
Karolin Luger, Ph.D., Chair
HHMI and Colorado State University
Karen Allen, Ph.D.
Steve Bryant, Ph.D.
National Center for Biotechnology Information/National Library of Medicine/NIH
Wah Chiu, Ph.D.
Baylor College of Medicine
Lila Gierasch, Ph.D.
University of Massachusetts, Amherst
Wim Hol, Ph.D.
University of Washington
Anne-Frances Miller, Ph.D.
University of Kentucky
William Montfort, Ph.D.
University of Arizona
Stephen H. White, Ph.D.
University of California at Irvine
Cathy H. Wu, Ph.D.
University of Delaware & Georgetown University Medical Center