General Information for Applicants
The production phase of the Protein Structure Initiative, known as PSI-2, consists of an interacting network with several components. The RFAs for support of the first two components have been issued and are summarized below.
The first RFA (GM-05-001) calls for applications for cooperative agreements to support large-scale structural genomics research centers. These centers perform every step of the structural genomics process, from DNA sequences to the high-throughput determination of a large collection of unique protein structures to meet the PSI-2 goals for structural coverage of most sequenced genes. Each large-scale center must develop technologies and methodologies that will make the production and structural determination of proteins less expensive, more efficient and more likely to be successful. Each center must also design a biomedical theme project for the determination of unique protein structures. NIGMS may fund three to five of these large-scale centers, each costing up to $12 million annually (total costs).
The second RFA (GM-05-002) calls for applications for cooperative agreements to support specialized structural genomics research centers. These centers will develop new methods, technologies, approaches and ideas for protein production and structural determination for classes of challenging proteins that are not currently amenable to high-throughput and that represent major bottlenecks in the structural genomics pipeline. Such classes of proteins include, but are not limited to, membrane proteins, small protein complexes and proteins from humans and other higher eukaryotes. The specialized centers will also produce and determine the structures of significant numbers of these proteins, especially in the later years of the project. NIGMS and NCRR may fund three to six specialized centers, each costing up to $4.5 million annually (total costs).
Program Highlights
General (Both RFAs)
- All research centers will be supported through cooperative agreements to foster coordination among the PSI-2 research centers and partnership with NIH staff. A Steering Committee composed of PSI principal investigator and NIH staff will make plans and coordinate target selection and other PSI-2 activities.
- Each research center should be an integrated, coordinated project with interdependent subprojects.
- The applicant institution must be a domestic for-profit or non-profit organization.
- Each research center application must have detailed plans for the management and administration of the research center and all subprojects.
- Each research center application must have detailed plans for the dissemination of experimental results, including timely deposition and release of structural coordinates and structure factors into the Protein Data Bank (PDB) upon completion of each structure.
Large-scale centers are responsible for:
- Determination of unique protein structures in high-throughput operation;
- Operation of high-throughput pipelines for all structural genomics tasks: protein family classification and target selection, protein production, sample preparation, structural determination and data analyses;
- Development of methodology and technology related to the goals of the research center;
- Inclusion of challenging proteins in production and structure determination and in target selection; and
- Analysis and dissemination of structural results.
Specialized centers are responsible for:
- Development of innovative methodologies and technologies for overcoming major bottlenecks in the structural genomics pipeline, especially classes of challenging proteins. These advances must:
- Provide wide applicability, portability and scalability;
- Make a major impact on the structural genomics pipeline and the PSI-2 goals; and
- At least approach high-throughput operation by the end of the project.
- Address major bottlenecks to high-throughput:
- Focusing on one or more classes of challenging proteins as identified in the RFA:
- Membrane protein;
- Higher eukaryote proteins, especially human; and
- Small protein complexes.
- As identified and justified by the applicant.
- Carrying out all components of structural genomics, but not necessarily in a high-throughput operation.
- Ramping up production and structural determination of challenging proteins in later years of the project.
Questions and Answers
Background Information
Q. Where can I find the report of the workshops that led to this initiative?
A. The summaries, recommendations and rosters for the workshops are posted on the NIGMS Web site at: http://www.nigms.nih.gov/Research/FeaturedPrograms/PSI/Meetings.htm.
Application
Q. Is there a special application form?
A. No. The standard PHS 398 form (rev. 5/04) should be used, but the special application requirements described in the RFA must be carefully observed.
Q. Are applications restricted to current investigators in the PSI pilot centers?
A. No. Both RFAs are open to all eligible applicants.
Q. May NIH staff assist an investigator in planning a project or finding collaborators?
A. No. NIH staff may provide PSI background information and respond to questions about the PSI program and RFAs, but staff members may not participate in planning a project or application.
Q. If an investigator is unsure whether to apply for a large-scale center or for a specialized center, may he/she submit similar and overlapping applications for both types of PSI-2 centers?
A. Yes. An investigator may apply for more than one of these PSI-2 centers, but the overlap must be noted and no more than one award may be made to the same principal investigator. This provision of the RFAs is not intended to encourage spin-off applications or non-overlapping applications from the same principal investigator, institutions or other major investigators.
Q. What is included in the page limit on the description of the research plan?
A. Both RFAs impose a page limit for the research plans, which include project overview, project rationale and subproject descriptions. This limit is 70 pages for the large-scale centers and 50 pages for the specialized centers. The special requirements are part of the research plan and thus included in the limit. Tables and figures are also included in this limit – with one exception. Both RFAs require the application to provide data on protein structures that have been solved by the participating investigators during the past five years. Since this table could be quite long, it will not be counted in the page limit.
Administration and Management
Q. Are the management, administration and direction of the large-scale and specialized centers of major importance?
A. Yes. The goal of coordinated direction of the PSI-2 requires each center to have an organized and well-developed plan for management, administration and direction, as well as appropriate resources and staff.
Intellectual Property
Q. What are the current NIH guidelines for investigators regarding intellectual property issues?
A. Guidance for extramural investigators regarding the use and exchange of "research tools" on the NIH Web site at http://www.nih.gov/od/ott/RTguide.htm. Applicants should develop plans for free and open access to results and information as well as the timely deposition and release of coordinates in the Protein Data Bank.
Eligibility
Q. May industry participate?
A. Industrial applications and collaborations are permitted, as long as all of the participating scientists understand and agree with the goals described in the RFA. In addition to the overall goals of structural genomics, the RFA requires that information and results be made public and protein structures be deposited in the Protein Data Bank and other databases in a timely manner.
Q. May foreign institutions apply?
A. Non-U.S. institutions may not apply for the cooperative agreements (U54) for research centers, but they may receive subcontracts as components of the research centers. Details on the NIH policy on foreign grants are given at http://www3.od.nih.gov/oma/manualchapters/grants/54104/
Review and Funding
Q. How will the Protein Structure Initiative research center applications be reviewed?
A. The applications will be reviewed by the NIGMS/NIH peer review system. The Office of Scientific Review, NIGMS, will convene a panel (or panels) of reviewers.
Q. Are site visits planned for these applications?
A. Site visits are not planned at this time; while selected site visits could be performed as part of the reviews, they would depend on constraints on timing, NIH staff and resources. Applicants should present a complete, well-justified proposal and not assume that site visits will occur.
Q. When will the reviews take place?
A. The first level peer review will likely occur in February or March, 2005. The second level of review by the National Advisory General Medical Sciences Council will take place in mid-May, 2005.
Q. When will awards be made?
A. Probably on July 1, 2005.
Q. How will funding decisions be made?
A. NIH staff will make these decisions based upon overall scientific merit and the overall contribution to the goals of the PSI-2 and the mission of NIGMS, with the advice and consent of the National Advisory General Medical Sciences Council.
Q. In addition to scientific merit and the availability of funds, the award criteria in the RFA include programmatic priorities. What does this mean?
A. It means that NIH staff will consider overall program goals in making funding decisions. For the large-scale centers, foremost among the program goals is target selection for structural coverage of sequenced genes and thus the inclusion of wide-ranging groups of proteins. As an example, the NIH staff might decide to fund an application focused on eukaryotes with a high, but not the best, priority score, if all of the top-scoring applications were focused on prokaryotes. For the specialized centers, a crucial goal is the methodology and technology development for each of the three named classes of challenging proteins and other classes of proteins for which the applicants have offered compelling justification. Similar to the previous example, an application focused on membrane proteins might be funded if it had a high, but not the best priority score and was the best application focusing on this class of proteins. Another factor in funding decisions might relate to regional distribution in order to take advantage of the resources and scientific talents found across the nation. Scientific and personnel overlaps will be examined carefully. No more than one award will be made to the same principal investigator and other major investigators. Funding of two centers at the same institution would require very strong justification.
Q. What are the other components of the PSI-2 Network and when will they be announced?
A. A third component, the disease-targeted structural genomics centers is being considered as a component of the NIH Structural Biology Roadmap. A final decision is expected later in 2004. A fourth component, the PSI Knowledge Base, will be organized after the PSI-2 begins in mid-2005.
Target selection
Q. How will the large-scale centers select their targets?
A. The first and third target selection goals (structural coverage of sequenced genes and consideration of targets proposed by the scientific community) are PSI Network activities. Each center must identify groups of proteins that the center will work on in meeting these goals. Under terms of the cooperative agreement, all PSI-2 centers will work with NIH staff to select targets to meet these goals and to determine each center’s tasks. The second goal (structural genomics research project with a significant biomedical theme) is an individual activity for the large-scale centers. Each center will select targets that will lead to unique, non-redundant protein structures that addresses the center’s chosen scientific problem.
Q. How will the specialized centers select their targets?
A. The targets must be representatives of sequence families and thus lead to the determination of unique and non-redundant protein structures. Although overall adherence to the PSI-2 goals is expected, the details of target selection might vary for different challenging proteins and thus for each specialized center. Each applicant is expected to propose plans for target selection.