RFA-GM-10-004: PSI:Biology Knowledgebase (U01)

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov/)

Components of Participating Organizations
National Institute of General Medical Sciences (NIGMS), (http://www.nigms.nih.gov/)

Title: PSI:Biology Knowledgebase (U01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-GM-10-004

Catalog of Federal Domestic Assistance Number(s)
93.859

Key Dates
Release Date: May 13, 2009
Letters of Intent Receipt Date: June 17, 2009
Application Receipt Date: July 17, 2009
Peer Review Date(s): October/November, 2009
Council Review Date: January, 2010
Earliest Anticipated Start Date: July 1, 2010
Additional Information To Be Available Date (Url Activation Date): May 1, 2009
Additional information about the PSI:Biology initiative will be available at http://www.nigms.nih.gov/Initiatives/PSI:Biology
Expiration Date: July 18, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This FOA solicits applications to maintain and enhance the PSI:Biology Knowledgebase in support of NIGMS PSI:Biology projects. The Knowledgebase will be one component of the PSI:Biology network. As a central information hub, the Knowledgebase plays a critical role in making the research of PSI:Biology widely available to other scientists and performs outreach activities to inform and solicit input from the scientific community to increase the impact of PSI:Biology. Applicants should propose specific plans to meet the objectives described in Part II- Section I: Funding Opportunity Description below. The awardee will become part of the PSI:Biology network Steering Committee and will work jointly with other investigators and NIH staff to manage the overall PSI:Biology initiative.
Mechanism of Support. This FOA will utilize the U01 cooperative agreement award mechanism.
Funds Available and Anticipated Number of Awards. The National Institute of General Medical Sciences expects to award up to $2.8 million annual total costs through this announcement. There will be one award.
Budget and Project Period. The expected budget range is up to $2.8 million total costs per year. The total project period for an application submitted in response to this funding opportunity is expected to be five years.
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Number of Applications. Applicants may submit only one application.
Resubmissions. Resubmission applications are not permitted in response to this FOA. Renewals. Renewal applications are not permitted in response to this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
Application Materials. See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
         1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
         3. Collaborative Responsibilities
         4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This FOA solicits applications to maintain and enhance the PSI-Structural Genomics Knowledgebase in support of the NIGMS PSI:Biology initiative and other related programs. The Knowledgebase will be one component of the PSI:Biology network. The network will also include Centers for High-Throughput Structure Determination, Centers for Membrane Protein Structure Determination, Consortia for High-Throughput-Enabled Structural Biology Partnerships, and the PSI-Materials Repository. As a central information portal, the Knowledgebase will play a critical role in outreach to make the PSI:Biology research output widely available to other scientists by maintaining key data on the operations of the PSI:Biology network and by providing links to a wide range of other information databases important to the community of biology researchers. The Knowledgebase will collect and organize in a readily useable manner a library of information of interest to both structural and non-structural scientists. The Knowledgebase will also enhance the impact of PSI:Biology research by promoting workshops to disseminate results and by soliciting input from the scientific community.

Established in 2007, the current PSI-Structural Genomics Knowledgebase serves as a portal to information developed by the PSI. This information includes links to protein structures deposited in the Protein Data Bank; protocols for cloning, expression, purification, and crystallization or preparation for NMR of genes whose structure has been undertaken by the PSI; a database of targets selected by the PSI and other structural genomics efforts around the world for structure determination; access to homology models prepared by other groups from template structures from the PSI; a list of structure and methods publications published by the PSI researchers; metrics of structural coverage for sequence families studied by the PSI; access to clones deposited by the PSI in the PSI Materials Repository; access to related publications, an entry portal for evaluating and proposing sequences for structure determination by the PSI; links to annotation data from other databases; and extensive education and outreach activities on behalf of the PSI. See the PSI-Structural Genomics Knowledgebase Web site for further information.

The current Knowledgebase may be continued, transferred to a new provider, or supplanted by a new Knowledgebase as a result of this competition. The PSI-Structural Genomics Knowledgebase name may be changed. Ideas and rationale for name changes are welcomed, but the final decision will be made by NIGMS staff.

Background

This FOA is part of a new NIGMS initiative, PSI:Biology (http://www.nigms.nih.gov/Initiatives/PSI/Biology/), that will be established through a series of five RFAs (Request for Applications) and three PARs (Program Announcements with on-going receipt dates and special review considerations but with no set-aside funds) over the course of the next several years. PSI:Biology represents a significant shift in focus for the PSI. The PSI was initiated in FY2000, after extensive dialog with the scientific community, with the ultimate goal of significantly advancing the protein folding problem (i.e., the relationship between the sequence of a protein and its three-dimensional structure). The first phase (PSI-1), FY2000-2004, tested whether the concept of high-throughput structure determination was viable and resulted in the development of new methods and technologies, and high-throughput pipelines for all steps along the pathway from targeted sequence to deposition of the solved structure in the Protein Databank (PDB). The second phase (PSI-2), FY2005-2009, applied high-throughput methods, such as those developed in PSI-1, to solve large numbers of proteins of novel structure, revealing new folds and illuminating families of proteins that had no previous representation in the PDB. The goal of PSI-2 was to cover sequence/structure space at a sufficient density that the structure of most proteins could be modeled reliably from their sequences and the known structures of their nearest neighbors in the database. See: http://www.nigms.nih.gov/Initiatives/PSI/ and https://grants.nih.gov/grants/guide/rfa-files/RFA-GM-05-001.html for extensive discussion of the initial goals of the PSI and of structural genomics in general.

A mid-course Assessment of the PSI was conducted on September 24, 2007. Among the main conclusions were: 1) that the PSI had been highly successful in establishing pipelines for protein production and structure determination, and had successfully solved large numbers of structures; and 2) that the PSI had made significant contributions to improve methodology and technology that had benefited structural biologists in general. However, there were concerns as well: 3) that the dissemination of results and materials had not been effective; 4) that the effort aimed at full coverage of sequence space was becoming an unattainable goal due to the rapidly accelerating pace of determining new sequences; and 5) that the focus on novel folds meant that structures were by and large divorced from known biological function. Thus, the impact of the PSI on the biological community at large was not as great as it could and should be.

Since the Assessment, the then recently established PSI-Structural Genomics Knowledgebase and PSI-Materials Repository have become more firmly established and efforts have been put in place to improve annotation of structures, improve the access to modeling capabilities, more clearly articulate the target selection strategy, and establish a centralized process for community nomination of targets. The goals and metrics of success have been carefully documented, and as of February 2009, more than 3,000 distinct structures have been solved. Efforts to improve dissemination have included over 1,200 publications. A centralized repository and set of processes have been established for reporting, validating, storage, and distribution of plasmids generated by the PSI centers.

As the end of PSI-2 on June 30, 2010 approaches, it has become clear that the goal of covering sequence space may not be achievable in the short term. However, it does not appear that fold-space or the number of single-domain family structures is unbounded and indeed, the PSI has gone a very substantial way toward completion of these more restricted coverage goals. The subject of sequence space coverage and of the leverage of solved structures (i.e., ability to provide models of sequences of unknown structure) has been reexamined and discussed at length. It appears useful to continue this effort, but at a reduced level of intensity and with focus on the more restricted biomedically significant regions of sequence space. The need to remarry structure and function has been recognized and increasingly plays a role in the current PSI through biological theme projects and collaborations. These changes in direction and emphasis will be accelerated as PSI:Biology comes into existence.

In anticipation of the end of PSI-2, NIGMS held a meeting to discuss Future Structural Genomics Initiatives on October 30-31, 2008. This meeting included a review of progress since the 2007 Assessment with a view to understanding the capabilities of high-throughput structure determination and the potential application of those capabilities to additional problems beyond the protein folding problem. The meeting included a balance between currently funded investigators of the PSI, other structural genomics investigators, and scientists from the structural biology and cell biology community at large. Among the recurring themes were: i) evolution of the intellectual drivers for structural genomics; ii) engagement of a broad scientific community in the selection of protein structural targets; iii) improvements in experimental and computational functional annotation; and iv) enhancing the utilization of the intellectual and material products of structural genomics through improved access, education, and dissemination. As captured in the chairperson's summary, "The panel was in uniform agreement that PSI-1 and PSI-2 have met many of the initial goals. In particular, new methods and technologies have been developed; high throughput structural pipelines have been set up in a number of centers; it has been demonstrated that macromolecular structures can be determined on the scale of many hundreds of structures per year, with both X-ray and NMR methods contributing; the cost per structure has fallen continuously; the range of previously unknown folds and protein families has been vastly enlarged; and several joint projects with biomedical communities have been established." The question then became how best to utilize this capacity in a way that will provide the greatest impact on biomedical science. The report included several specific topic suggestions as covered below. The report also emphasized the need for continuing technology development, increased outreach to the biomedical community, and the establishment of mechanisms that support PSI activities and interface with the wider biological community.

The report of the Future Structural Genomics Initiatives meeting, along with progress reported at the PSI Annual Meeting on December 10-11, 2008, were considered by the PSI Advisory Committee (PSIAC), and reported to the National Advisory General Medical Sciences Council, at its meeting on January 22-23, 2009, along with the report of the Meeting of the PSI Steering Committee. The Report of the PSI Advisory Committee and their Recommendations for the Future of the PSI set the stage for the new PSI:Biology initiative.

The PSIAC emphasized the value that had been created through PSI-1 and PSI-2, "The PSIAC has followed the evolution of PSI-1 and PSI-2 closely and observed the impressive development of a new type of science: large teams working in a cooperative fashion, with clearly articulated goals, and with close management by NIGMS staff. The capacity of the resulting large PSI centers to carry out high-throughput structure determination is truly stunning, and the accomplishments from eight years of effort are outstanding in terms of numbers of new structures. Particularly impressive are the number of novel folds and the resulting impact on fold space, as well as the technological enhancements that enable high-throughput structure determination and consequently touch the entire field of structural biology. Moreover, the existing large-scale centers established as a result of PSI-1 and PSI-2 represent a new resource, unknown before the PSI, and one that changes what our scientific enterprise is capable of from 2009 forward."

The PSIAC made a number of recommendations about how the PSI might be restructured and refocused, including realigning the mission of any large scale centers to focus on biologically important questions that would be pursued in partnership with the broader community of scientists. They felt that a number of components of the current PSI could be satisfactorily competed and supported through program announcements, rather than RFAs; specifically, technology developments for specific stages in the determination of protein structures and methods for improving homology modeling could be supported using program announcements. They emphasized the overwhelming importance of membrane proteins and the continuing huge lag in the number of structures solved relative to soluble proteins. Finally, they recommended continued support for the PSI-Structural Genomics Knowledgebase and PSI-Materials Repository, coupled with increased outreach and dissemination efforts by all components of the PSI. Based on the above recommendations, NIGMS staff presented a Concept Clearance document to the Council, and the Council approved those plans, which are being implemented as outlined below.

Organization of the PSI:Biology Initiative for High-Throughput Structural Biology

The goal of the PSI:Biology initiative will be to test whether the new paradigm of high-throughput structure determination via highly organized networks of investigators can be applied to a broad range of biological problems. It will consist of five main components, established through RFAs with set-aside funds soliciting applications for Cooperative Agreements: 1) Centers for High-Throughput Structure Determination; 2) Centers for Membrane Protein Structure Determination; 3) Consortia for High-Throughput-Enabled Structural Biology Partnerships; 4) the PSI-Structural Genomics Knowledgebase; and 5) the PSI-Materials Repository; plus three additional components supported through on-going PARs: a) Technology Development for High-Throughput Structural Biology Research; b) Technology Development for Protein Modeling; and c) High-Throughput-Enabled Structural Biology Research. These components will function as follows.

Requests for Applications

The core of the PSI:Biology network will be created through five FOAs that will establish cooperative agreements. These will be managed collectively through a steering committee that will include representatives of each of the components and NIH staff.

The Centers for High-Throughput Structure Determination (RFA-GM-10-005) will have five main functions: i) determination of protein structures utilizing high-throughput pipeline capabilities; ii) development of technology to improve the pipeline and to attack increasingly difficult proteins and complexes of proteins at high throughput; iii) bioinformatics analysis of potential targets, solved structures, and the creation of models based on solved structures; iv) dissemination of information and materials via the Materials Repository and Knowledgebase; and v) collaborative research with other members of the network to be established through this and the other RFAs and PARs that are part of this initiative. These centers will receive the majority of their operating budgets directly through RFA-GM-10-005. That budget will support the core activities of the center. It will include support of center infrastructure that will enable the collaborative research to be solicited through RFA (RFA-GM10-007) and the solution of community-nominated targets to be submitted through the Knowledgebase. It will also provide support for continuing work on coverage of sequence space and any biological theme project associated with the center. The centers will receive additional budget components through the remaining programs of the initiative to enable them to scale up specific activities to meet the needs of their collaborators. Overall activities of these centers are expected to be 70% collaborative research in conjunction with awards issued through RFA-GM-10-007 and community-nominated targets, 15% biological theme research, and 15% sequence coverage and technology development related research. In addition to depositing vectors and clones into the Materials Repository, it is expected that the centers will make proteins available for investigations that complement their structural studies.
The Centers for Membrane Protein Structure Determination (RFA-GM-10-006) will focus on the solution of membrane protein structures of high biological interest and on the development of new methods expected to render membrane protein structures more amenable to high-throughput structure determination. Within the realm of membrane protein structures, these centers will have similar responsibilities to the above centers for: i) determination of structures; ii) development of technology; iii) bioinformatics analysis and modeling to leverage solved structures; iv) dissemination of information and materials; and v) collaborative research. These centers, however, will receive the major component of their budget through RFA-GM-10-006, with lesser amounts expected to come through collaborative arrangements. Overall activities of the membrane protein centers are expected to be 70% research on biological targets proposed by the centers and 30% on targets developed through collaborations solicited through RFA RFA-GM-10-007 and community nominations.
Consortia for High-Throughput-Enabled Structural Biology Partnerships (RFA-GM-10-007) have the primary purpose of ensuring that a broad community of scientists participates in and benefits from high-throughput structural biology. Applications will be solicited from individuals and groups of scientists who are not associated with the above centers (established by RFA-GM-10-005 and RFA-GM-10-006) and who propose to collaborate with the network as a whole, not a single specific center. Individuals affiliated with the above centers (established by RFA-GM-10-005 and RFA-GM-10-006) may also participate in these applications, but may not be the sole or dominant group of investigators. Scientific problems proposed should make effective use of the high-throughput capabilities of the centers or provide a driver for further technology development. These consortia are expected to include functional characterization of proteins primarily outside of the structure determination centers as well as structure determinations within these centers and thus provide a key link between a structure and its biomedical impact. Budgets and durations of these projects (typically 2-5 years; average = 3 years) will vary depending on scope as will the division of funds to support activities within the above centers and activities outside the centers. In general, less than half of the collaborative budget will go to support structural center operations. Investigators participating in these consortia are expected to abide by the PSI policies regarding identification of targets and timely distribution of materials and results as described under the "Cooperative Agreement Terms and Conditions of Award" that are discussed in Section VI.2.A "Award Administration Information". Co-funding by other Institutes and Centers of the NIH for structural studies relevant to their missions will be solicited.
The PSI-SG Knowledgebase (RFA-GM-10-004), i.e., this FOA, will play an increasingly important role in information dissemination and coordination of activities across the network. It will continue to provide information on targets, project progress, materials and methods, raw structure data and coordinates via the PDB, enhanced annotation of protein function, a portal to models generated from existing experimental data, and additional links. It will provide the community access to nominate targets for structure determination and will continue to foster an awareness of structural genomics and structural biology to the wider scientific community.
The PSI-Materials Repository will continue to play a key role to provide centralized collection, maintenance, storage, and distribution of vectors and clones generated by the PSI. As more clones and structures are produced, the PSI-MR will continue to serve and enable researchers throughout the country and the world to receive access to these valuable reagents.

Applications for the first four above components are all being solicited for start dates in the summer, 2010. Because the existing PSI Materials Repository is funded through FY2010, that component of the network is not being competed until next year.

Program Announcements

Recognizing that not all of the best ideas may be ready for submission on a single RFA receipt date or conceived only in large-scale centers, and recognizing the need for continued support of some projects evolving from the current specialized centers, it is planned to issue a series of PARs (program announcements with on-going receipt dates and special review considerations, but no set-aside funds) to allow for the fluid addition of new projects and investigators to the network as opportunities emerge. These PARs will provide for on-going peer review of applications using traditional (R21, R01, and P01) grant mechanisms for investigators who wish to conduct research in association with the network. The applications might or might not build on existing collaborations in the network. Independent projects will be welcomed in response to these PARs, but investigators will be expected to participate in network activities. Depending on the scope of the project and the need for NIH staff involvement to assure the effective participation of awardees in the overall PSI:Biology initiative, conversion to cooperative agreement mechanisms may be warranted and will be negotiated at the time of award.

Technology Development for High-Throughput Structural Biology Research (PAR to be announced) is needed particularly for the study of membrane proteins, proteins that form complexes, nucleic acids, and protein-nucleic acid complexes, and for improvements to the technology for high-throughput operations.
Technology Development for Protein Modeling (PAR to be announced) is needed to improve the leverage of experimentally-determined structures, to improve the ability to solve structures with sparse experimental constraints, and to make modeling more accessible and transparent to non-experts in the field.
High-Throughput-Enabled Structural Biology Research (PAR to be announced) opportunities are expected to ripen over time as the broader community becomes aware of the PSI:Biology network. It is critical that the door remain open for new projects to gain access to the latest high-throughput capabilities. Projects responsive to this PAR will be similar to those solicited through RFA-GM-10-007.

The first two of the above PARs will be competed in parallel with the above RFAs. The first competition under High-Throughput-Enabled Structural Biology Research will be delayed by several months after RFA-GM-10-007 so that applications for the RFA and for the PAR will not be in competition.

The estimated budgets for each component of the PSI:Biology initiative are included in each of the RFAs and in the Concept Clearance. The overall budget for PSI:Biology is expected to be at least $37.7 Million and may by as high as the current PSI budget of $69.9 Million, depending on the number, quality, and size of the applications, under current budget predictions. The overall budget for awards through the three PARs will be open-ended as applications in response to these FOAs will be in competition with all other applications assigned to NIGMS.

Objectives of this FOA

This FOA specifically solicits applications to maintain and enhance the PSI-Structural Genomics Knowledgebase or its successor (hereinafter Knowledgebase) in support of the PSI:Biology initiative. The Knowledgebase will serve as an electronic portal to PSI:Biology projects for the scientific community. All participating components of PSI:Biology will be highly integrated and synchronized in their efforts to contribute to the program mission. As a supporting pillar of the PSI:Biology program, the Knowledgebase plays a fundamental role in this integration and synchronization. Listed below are the main functions of the Knowledgebase in priority order.

Structural Genomics Information Repository and Web Portal

The PSI:Biology network members will be required to make their data and research resources available to the public through a central information repository. This is the foremost function of the Knowledgebase. It must continuously develop capabilities to accommodate heterogeneous types of information and large amounts of data. The Knowledgebase is a central point-of-entry for accessing all the information and resources related to PSI:Biology and a portal to resources outside of the PSI. It will continue to develop user-friendly interfaces and tools for retrieval and analysis of structure and structure-related information from a variety of sources. The Knowledgebase must maintain and enhance tools for easy access to information concerning experimental materials from the PSI:Biology efforts as well as links to the clones made available by the PSI-Materials Repository. The Knowledgebase will be expected to collaborate with researchers in the structural genomics and structural biology community to develop standards and a unified format in information gathering, organization, and presentation. The Knowledgebase must continue to provide support for the TargetDB (http://targetdb.rcsb.org) and PepcDB (http://pepcdb.rcsb.org). All activities of these databases will continue to be handled by the Knowledgebase. In addition, the Knowledgebase will continue to host a PSI Investigators Intranet website to facilitate communication among the PSI:Biology network investigators.

Structural Genomics Target Management

The Knowledgebase will provide detailed information on the targets selected by the PSI:Biology network members and other structural genomics projects, with the inclusion of sequence, family size and composition, links to annotations and functions of the family members provided by other databases, status of the targets, and other information proposed by the applicant. Dynamic and schematic illustrations must be provided to demonstrate the projected and current progress in covering the sequence space by selected and solved targets respectively. The mechanism to invite community participation in target nomination must be maintained and enhanced in collaboration with the PSI:Biology Research network. For the current community nomination process, see: http://kb.psi-structuralgenomics.org/KB/targetlogin.jsp.

Structural and Functional Annotation

The applicant will establish collaborations with the PSI:Biology network members and partnerships to develop a system of structural and functional annotation for the structures determined by PSI:Biology efforts. The Knowledgebase will not be responsible for performing annotations. Instead, the Knowledgebase maintains and enhances the user-friendly environment for deposition and query of the annotations generated by PSI:Biology projects and other sources of annotation. Links to publications and annotations at other databases will be continuously expanded. Continuing to facilitate community (outside the PSI:Biology network members) participation in annotation is another requirement. The applicant needs to be creative in proposing incentives to community information providers and moderators that will likely be effective in promoting community participation. Quality assurance mechanisms for annotation must be enhanced. For the current Knowledgebase annotation functions, see: http://kb.psi-structuralgenomics.org/KB/index1.jsp?pageshow=39.

Computational Modeling Support

Computational modeling of protein structures plays an essential role in reaching the goals of structural genomics. The Knowledgebase must provide support in this area by continuing to provide easy access to high-quality models of proteins that are in the sequence families covered by the structural genomics targets. The applicant will collaborate with the modeling community to develop filters and assessment criteria that only allow the best available models to be selected for posting. These models will be presented with a designation of quality/confidence levels and potential utilities. The Knowledgebase should not collect and present all computational models without discretion. The applicant must have plans for continually reevaluating and improving model assessment methods and promoting the most promising models. The Knowledgebase must also provide links to modeling tools and servers developed by other groups, potentially allowing users to generate models using these tools, and support the development of computational model quality evaluations and uncertainty estimations for users. For the current Knowledgebase models link, see: http://kb.psi-structuralgenomics.org/KB/index1.jsp?pageshow=38.

Training and Education Coordination

The Knowledgebase will be required to coordinate with the PSI:Biology network members to develop workshops and training courses and to participate at scientific community national meetings for active knowledge dissemination. The collaboration with Nature Publishing Group and the Knowledgebase Nature Gateway or a comparable project with a similar organization must be maintained and enhanced. Continuing innovation in methods for outreach and education about the PSI and structural biology in general is required of the Knowledgebase.

Progress Analysis

The Knowledgebase will develop and report metrics, as approved by the PSI:Biology Network Steering Committee, that can be used to analyze periodically the progress of the PSI:Biology projects and their impact on biomedical research, including but not limited to, the metrics of coverage of sequence space by the PSI:Biology projects. For the current Knowledgebase progress metrics page, see: http://kb.psi-structuralgenomics.org/KB/index1.jsp?pageshow=40.

Data Archiving

The Knowledgebase will not be responsible for archiving biochemical and functional characterization data generated by the PSI:Biology network, except as required for the TargetDB and PepcDB, or as subsequently mutually agreed upon through negotiations between the Steering Committee, the Knowledgebase, and NIH staff. The Knowledge base will however provide a portal to other databases that provide for appropriate archival of such data, such as are linked under Annotations. http://kb.psi-structuralgenomics.org/KB/index1.jsp?pageshow=39

Other Activities

Applicants may also propose other activities or plans that will enhance the value of the Knowledgebase and better support the structural genomics and structural biology research communities without duplicating existing efforts.

In addition to the main functions enumerated above, other requirements for the Knowledgebase include adaptability, interoperability, sustainability, portability.

Adaptability

The Knowledgebase must be able to adapt continually to new knowledge, technology, and requirements of the structural genomics and structural biology communities. It is expected that the Knowledgebase will continue to develop innovative solutions to changing needs of the PSI:Bology network and the broader scientific community.

Interoperability

The Knowledgebase must further develop the capability of interconnecting to various other resources. Direct links between the resources at other pertinent databases and at the Knowledgebase must be maintained and enhanced, so that complementary data and tools will be easily accessible to users of these databases. To minimize overlap and to establish interoperability with existing resources, the applicant must describe plans to enhance collaboration with other resources proposed by the applicant.

Sustainability

The applicant must present plans to sustain and maintain the operability of the Knowledgebase, including personnel changes and disaster recovery (refer to Section IV below).

Portability

The Knowledgebase will provide long-term support to the research community. At the end of the funding period, the NIGMS may consider re-announcing the program for open competition. The successful applicant of the current RFA must present plans in architecture design and software development practices that will make the entire Knowledgebase and its components easily transferable to other groups for continued maintenance and further development. All products developed with support of this program must be made readily transferable consistent with achieving the goals of this program and applicable NIH policies. Applicants must state explicitly in the application their willingness to provide for continued availability of the Knowledgebase for further development and access by the research community.

The applicant must also demonstrate their capacity for vision, their willingness to participate in the PSI:Biology network, their ability to engage in community consultation, and willingness to share software as outlined below.

Vision

Plans by the applicant to continuously expand the information content of the Knowledgebase to include information not specifically a part of PSI:Biology should be detailed in the application. Examples would include annotations of structures, links to from other existing databases of proteins and genes and scientific Wikis.

Participation in the PSI:Biology network

The Knowledgebase is one component of the PSI:Biology network. The Director of the Knowledgebase will be a voting member of the PSI:Biology Network Steering Committee. The Knowledgebase Director must be committed to participating in the network managerial activities, including monthly conference calls and an annual meeting at the NIH. The Knowledgebase Director must be actively involved in shaping the policies and programs of the PSI:Biology project through participation on the PSI:Biology Network Steering Committee. The Knowledgebase Director must also implement decisions arrived at by the Steering Committee. The Knowledgebase Director must comply with the Terms and Conditions described in Section VI.2.A.

Community Consultation

The applicant must have plans to solicit suggestions and advice from the research community that the Knowledgebase serves. As an example, the Knowledgebase Director must form an External Advisory Committee (EAC) to help advise the Knowledgebase Director on issues related to the Knowledgebase including matters of particular interest to the community. The EAC should meet at least annually and annually provide a written report to the Knowledgebase Director. Representatives from NIGMS may be invited to attend meetings of the EAB at the Knowledgebase Director’s discretion. Overall evaluation of the Knowledgebase will be carried out by the PSI Advisory Committee (PSIAC) on an annual basis.

Software Sharing

Software developed by the Knowledgebase is expected to be freely available to all biomedical researchers and educators for research purposes. The terms of the software availability should permit the commercialization of enhanced or customized versions of the software or incorporation of the software or pieces of it into other software packages. The terms of software availability should also include the ability of researchers outside the Knowledgebase to modify the source code and to share modifications with other colleagues as well as with the Knowledgebase.

PSI:Biology Network Operations and Governance

All awarded components of the PSI:Biology initiative, including the Knowledgebase, will become part of a network of researchers that will be governed by the "Cooperative Agreement Terms and Conditions of Award" that are discussed in Section VI.2.A "Award Administration Information." A single overall PSI:Biology Network Steering Committee (Steering Committee) will be responsible for overall governance. A PSI Investigators Intranet website to be maintained by the Knowledgebase will facilitate communications among PSI:Biology network investigators.

External Input to the network

The PSI Advisory Committee will provide external input to the PSI:Biology Network Steering Committee and to NIH staff on all components of the network including the Knowledgebase. In addition, the Project Director/Principal Investigator of the Knowledgebase will appoint an External Advisory Committee for the Knowledgebase. This committee will report to and advise the PD/PI of the Knowledgebase on operations specific to the Knowledgebase.

Commitment to Diversity

The NIH and the NIGMS are committed to promoting and advancing the diversity of the scientific workforce. See: http://www.nigms.nih.gov/News/Reports/workforcediversity_100307.htm. Applicants responding to this initiative must propose creative ways to enhance and/or successful ways to ensure the continued diversity on their research teams. Reports from the National Science Foundation and the National Academy of Sciences emphasize the need for a well-trained scientific workforce that reflects the diversity of our nation. African Americans, Hispanic Americans, American Indians, and Natives of the US Pacific Islands are particularly underrepresented in the biomedical and behavioral sciences. Individuals with disabilities and individuals from disadvantaged backgrounds may also be underrepresented. The PSI:Biology research groups should reflect the resolve of the NIH and NIGMS to enhance the diversity of the scientific workforce.

Data and Resource Sharing under this Initiative

A central feature of the PSI:Biology initiative is the sharing of data through the PSI-Structural Genomics Knowledgebase and sharing of research resources through the PSI-Materials Repository and by other mechanisms. The Knowledgebase must accept, store and provide this data to the broader scientific community in a timely and readily usable manner. Details of these requirements are described under the Cooperative Agreement Terms and Conditions of Award that are discussed in Section VI.2.A "Award Administration Information".

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the U01 cooperative agreement award mechanism(s).
The Principal Investigator (PI) will have primary responsibility for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see https://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". Projects funded as cooperative agreement projects may be continued beyond the initial award period through application for an award in response to any appropriate FOA. Plans to reissue this FOA in the future are indefinite.

2. Funds Available

The National Institute of General Medical Sciences intends to commit up to $2.8 million dollars in total cost in FY 2010 to fund one award in response to this FOA. An applicant may request a project period of up to five years.
One award will be made assuming an application of sufficient merit is received.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

NIH grants policies as described in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see https://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may only submit one application.

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are not permitted in response to this FOA.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

RFA-GM-10-004 PSI:Biology Knowledgebase (U01)

Foreign Organizations (Non-domestic (non-U.S.) Entity)

Foreign Organizations are NOT eligible to apply. However, applications from domestic organizations may include a foreign component through a consortium arrangement. Policies governing awards to domestic organizations with a foreign component will apply to such consortium arrangements.

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications including foreign consortium component must:

Request budgets in U.S. dollars.
Contain detailed budgets. See NOT-OD-06-096.

In addition:

Charge back of customs and import fees is not allowed.
Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF.
Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., “Administrative and National Policy Requirements”

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: June 17, 2009
Application Receipt Date: July 17, 2009
Peer Review Date(s): October/November, 2009
Council Review Date: January, 2010
Earliest Anticipated Start Date: July 1, 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the Principal Investigator
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Peter C. Preusch, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive
Building 45, Room 2AS-13C, MSC 6200
Bethesda, MD 20892
Telephone: (301) 594-0828
FAX: (301) 480-2004
Email: preuschp@nigms.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Helen R. Sunshine, Ph.D.
Office of Scientific Review
National Institute of General Medical Sciences, NIH
45 Center Drive, Room 3An.12F, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-2881
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

Expenditure of funds under this award will be subject to the Cooperative Agreement Terms and Conditions of Award described below.

6. Other Submission Requirements

For cooperative agreements, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Participant Affiliations:

Applications must include a separate page that lists 1) all participants of the application, including consultants and collaborators; 2) all the institutional affiliations for each participant; 3) their roles on the project; and 4) the person months effort listed separately for each role. This requirement will facilitate the review of applications.

Research Plan Page Limitations

The overall application should not exceed 25 pages for the Research Plan Sections, Items 2-5 (Specific Aims, Background, Preliminary Results, and Research Plan including the specifically mentioned sections described below). Please note that there is no requirement to submit the maximum number of pages; instead, concise, articulate applications are desired. The application should include in order: Face Page (Form Page 1); Summary Page (Form Page 2); Participant Affiliations page mentioned above; Table of Contents (Form Page 3); Consolidated Detailed Budget for the Initial Budget Period (Form Page 4) and Consolidated Budget for the Entire Proposed Project Period (Form Page 5), followed by subproject and consortium budget details for the initial year and the entire project period; biographical sketches for all key personnel; institutional support, resources and facilities; the research plan as described below; followed by other components as needed according to the directions provided in the PHS 398 application, including details of consortium arrangements and letters of collaboration. The Research Plan should address all of the functions of the Knowledgebase described under the Purpose section of this RFA.

Management Plan: Applications must include a project management plan, which may include the Multiple PD/PI Leadership Plan as a subheading (if the application is designated a Multiple PD/PI application). Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information" and should explain how they plan to meet these terms and conditions. Applicants must indicate their willingness to participate in the PSI:Biology Network Steering Committee and how they anticipate managing the interactions between the Knowledgebase and members of the PSI:Biology network. The Knowledgebase Director must plan to appoint an External Advisory Committee. Although the plan should be set forth, names of potential members should not be included. Potential members should NOT be contacted, named, or appointed until after an award is made. If the investigators are now or have been involved in previous projects with advisory structures, however, the names of present and recent past advisors should be identified in the Participant Affiliations page described above. The Knowledgebase Director should plan for an annual meeting that brings all participating investigators together and provides an opportunity for External Advisory Committee review. Other means for frequent communication should also be described. The management plan should address how the Knowledgebase will go about priority setting, redistribution of resources, personnel, and space, and other management issues.

Plan for Increasing Researcher Diversity: Applicants must propose ways to reflect the NIH and NIGMS commitment to enhancing the diversity of the scientific workforce.

Research Training Plan: Applicants must explain how the activities of the Knowledgebase will contribute to the training of graduate students, postdoctoral researchers, and other scientists and how these activities will be supervised.

Research Resource Sharing Plan: Describe plans for research resource sharing in addition to the activities described under the Cooperative Agreement Terms and Conditions of Award. Since one major goal of the Knowledgebase is to make research data from the PSI:Biology network available to the wider community, the application should describe in detail plans for continuing and enhancing this function of the Knowledgebase.

Intellectual Property Plan: An institution's stance on intellectual property must be consistent with the goals of advancing and not hindering future research.

Budget:

The budget of total costs for the first year that includes direct costs, consortium/contractual costs, and facilities and administrative costs is up to $2.8 million. Annual cost-of-living increases in subsequent years should not exceed 3%. The budget should include funds for attending the PSI:Biology annual meetings and PSI:Biology Network Steering Committee meetings, and for co-organizing technical workshops and annual Knowledgebase External Advisory Committee meetings. The applicant should budget funds for travel for the purpose of outreach and education and for convening and attending relevant workshops, scientific meetings, conferences and other appropriate venues in support of outreach activities of the Knowledgebase. The budget should include any sub-awards or contracts for all components of the Knowledgebase such as the Technology portal, Annotation portal, Modeling portal, Publication portal and other necessary components, or their equivalents. It is expected that the Knowledgebase will maintain the relationship with Nature Publishing Group as a Gateway or will develop a similar arrangement, possibly with another organization; funds for this component must also be included in the budget.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. See https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html. Include five identical CDs in the same package with the copies of the application that are submitted to NIGMS.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and https://grants.nih.gov/grants/gwas/.

Resource sharing plans of the PSI:Biology initiative go beyond the NIH policies described above and are included in the Cooperative Agreement Terms and Conditions described below.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIGMS and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score.
Receive a written critique.
Receive a second level of review by the National Advisory General Medical Sciences Council.

The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined by peer review
Availability of funds
Relevance of the proposed project to program priorities
Compliance with PSI:Biology data and resource sharing policies and other special terms and conditions that differ from the agency's usual terms and conditions. See Section IV.5, “Funding Restrictions” and Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

How effective will the proposed Knowledgebase be in coordinating PSI:Biology projects and disseminating the resulting data to the broad scientific community? Does the application address all the required objectives of the Knowledgebase? Are the additional tasks proposed by the applicant significant?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the PI demonstrate the potential to be an interactive and effective member of the PSI:Biology network? Does the PI have the broad familiarity with outreach, data systems, software, and user interface to data necessary to meet the needs of the Knowledgebase? Does the PI have the administrative skills, experience, and/or potential to manage a project of the proposed scope?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In particular, are there innovative features in the design of model quality assessment methods and mechanism for community participation in functional annotation?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Does the applicant propose plans to address the issues of adaptability, interoperability, sustainability, and portability of the Knowledgebase? Are those plans specific and likely to be effective in achieving the goals? How feasible are the plans to invite community participation in target prioritization and functional annotation? Is the approach for model quality assessment well conceived and likely to be successful in selecting the best models and promoting utilization of the models? Is the community consultation plan acceptable? Is there sufficient evidence that the proposed Knowledgebase will be an integral component of the PSI:Biology network? Is the plan to coordinate and collaborate with other related databases clearly laid out? Is the software sharing plan consistent with the source code availability requirements? Do milestones identify key indicators and a time frame that will demonstrate significant progress for the project? Is the priority-setting plan appropriate for the project?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

In addition to the above review criteria, the following criteria will be applied to applications in the determination of the overall scientific merit and the impact/priority score.

Management Plan: Is an adequate plan presented to assure the productive and collaborative functioning of the center and its interactions with other components of the PSI:Biology network?

Research Training Plan: Is an adequate plan presented to assure that graduate students and postdoctoral researchers associated with the Knowledgebase receive appropriate scientific training? Are adequate plans presented to provide additional training and outreach activities to the scientific community at large?

Data Sharing/Dissemination Plan, Resource Sharing Plan, and Intellectual Property Plan: Are these plans adequate to assure that the Cooperative Agreement Terms and Conditions of Award will be met? Do they include additional activities that strengthen the application?

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations. As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications Including Foreign Components. Reviewers will assess whether the foreign component presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

The earliest anticipated award date will be in July 2010.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for

Design and direction of the project
Setting goals and milestones for the project
Committing sufficient effort to the project consistent with the scope of the Knowledgebase activities
Participating as a member of the PSI:Biology Network Steering Committee (Steering Committee)
Participation in cooperative agreement activities and acceptance of policies, plans, and decisions developed by the Steering Committee
Attendance at annual meetings of the Steering Committee and participation in its activities, including setting goals and making future plans
Participation in the activities of the PSI:Biology network, such as collective outreach efforts, presentation at national meetings, and other efforts to enhance network communication and dissemination
Ensuring the timely dissemination of information to the scientific public
Ensuring compliance with the intellectual property policies of the awardee institutions, the NIH, and the PSI:Biology network
Submitting periodic progress reports as specified in the Notice of Award. In addition to annual reports to NIH staff, the Knowledgebase Director will be expected to submit monthly reports to be shared with other PSI:Biology network investigators.
Appointing an External Advisory Committee of research scientists not involved in the Knowledgebase to provide independent assessment and advice to Principal Investigator
Inviting the PSI:Biology Network Director and other Scientific Liaisons and Program Officials to attend annual meetings of the Knowledgebase investigators and the External Advisory Committee. At the discretion of the Principal Investigator, portions of the External Advisory Committee meeting may be closed to NIH staff.
Cooperating with NIH staff, advisory groups, and other NIH designated evaluators by providing requested information, facilitating site visits, and otherwise assisting with efforts to assess progress of the center and the overall PSI:Biology initiative.

The awardee will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

An NIGMS Scientific Liaison will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

The PSI:Biology Network Director

The PSI:Biology Network Director will be NIH extramural staff member with leadership responsibilities for the management and coordination of the overall PSI:Biology initiative. The PSI:Biology Network Director will be a voting member of the PSI:Biology Network Steering Committee (Steering Committee) but will not direct the scientific activities of any of the PSI:Biology components (whose direction is the responsibility of the Principal Investigator).

The PSI Network Director will:

Provide advice to the Steering Committee on the overall direction of the PSI:Biology initiative and on setting and meeting its goals and milestones
Report on the PSI:Biology network activities and progress to the Director of NIGMS, the NIGMS Advisory Council, and advisory councils for other participating NIH institutes and centers
Appoint members and a chair of the PSI Advisory Committee, following consultation with the Director of NIGMS
Evaluate and implement the advice of the PSI Advisory Committee and the Steering Committee for allocating NIH support and for setting and revising PSI:Biology policies
Facilitate communication with the scientific community
Ensure that the Steering Committee and the PSI Advisory Committee address issues and concerns raised by the community.
Call and coordinate meetings of the Steering Committee and the PSI Advisory Committee
Attend annual meetings of the Knowledgebase investigators and the External Advisory Committee as time permits and at the invitation of the Principal Investigator
Coordinate assessment activities by NIH staff, the PSI Advisory Committee, and other NIH designated evaluation groups
Select appropriate additional programs to be added to the PSI:Biology network and new members of the Steering Committee as additional awards are made.

The PSI Network Director will not also serve as the program official for any component of the PSI:Biology network.

NIH Scientific Liaisons

The NIH Scientific Liaisons will be members of the NIH extramural staff who will serve on the PSI:Biology Network Steering Committee and have substantial scientific/programmatic involvement in the project that is above and beyond normal program stewardship. Each of the NIH institutes and centers supporting the PSI:Biology network will have one Scientific Liaison. Additional Scientific Liaisons may be assigned as necessary to work with specific components of the PSI:Biology network. A single NIH staff member may serve as the liaison to more than one component of the PSI:Biology network. An NIH staff member will be appointed as the scientific liaison to the Knowledgebase.

The Scientific Liaisons will:

Serve as voting members of the Steering Committee and attend all meetings
Assume a substantial coordinating role on the Steering Committee
Make recommendations to the Steering Committee based upon their knowledge of other, related NIH-supported research and resource activities
Facilitate interactions among the Steering Committee, the PSI Advisory Committee, and NIH staff
Provide advice and guidance to the Steering Committee to assure that the PSI project adheres to the NIH/NIGMS rules and regulations
Prepare reports to NIH management on the progress of PSI:Biology initiative components as needed
Attend annual meetings of the Knowledgebase investigators and the External Advisory Committee as time permits and at the invitation of the Principal Investigator
Take on additional responsibilities as negotiated at the time of award.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Scientific Liaison to any component of the PSI:Biology network may not also serve as the program official for another component.

NIH Program Directors

The NIH Program Directors are the extramural staff individuals who provide normal program stewardship for the PSI:Biology network awards. The NIH Program Directors are not members of the Steering Committee and do not direct the scientific activities of the PSI:Biology network awards (whose direction is the responsibility of the Principal Investigator).

The NIH Program Director will:

Negotiate goals and milestones with the awardees
Attend meetings of the Steering Committee as observers
Review annual reports on the progress of PSI:Biology initiative components
Provide information to the Principal Investigators on activities and policies of the PSI:Biology network and the NIH
Recommend appropriate budgets for the Knowledgebase, including withholding or reduction of support for failure to meet milestones and/or other terms or conditions
Sign-off on checklists for awards
Attend annual meetings of the Knowledgebase investigators and the External Advisory Committee as time permits and at the invitation of the Principal Investigator

The assigned program director for a component of the PSI:Biology network may not also serve as a Scientific Liaison for another component.

2.A.3. Collaborative Responsibilities

PSI:Biology Network Steering Committee

The PSI:Biology Network Steering Committee (Steering Committee) will be the main governing body of the PSI:Biology network. Membership will include the Project Directors/Principal Investigators of the High-Throughput Structure Determination Centers, the Centers for Membrane Protein Structure Determination, the Consortia for High-Throughput-Enabled Structural Biology Partnerships, the PSI-Structural Genomics Knowledgebase, and the Materials Repository, the NIH Scientific Liaisons, and others as nominated by the PSI:Biology Network Director. The NIGMS/NIH Scientific Liaisons will serve as voting members of the Steering Committee and attend its meetings. Total NIH representation on the Steering Committee will make up no more than 40% of the voting members. Other members of the NIH staff may also attend the Steering Committee meetings. The Principal Investigators of other national and international structural genomics projects may be added to the Steering Committee as non-voting members, as determined appropriate by the PSI:Biology

Network Director. The Knowledgebase will provide communications support for the activities of the Steering Committee and assist in implementing policy decisions of the Steering Committee and of NIH staff.

The Steering Committee will:

Coordinate and make decisions to ensure meeting the milestones and goals for the PSI:Biology initiative
Coordinate and make decisions on target selection and distribution to the network structure determination centers
Elect a chair, not to be an NIH staff member, to serve a 2-year term
Organize and appoint appropriate subgroups as may be needed to address network management issues and specific scientific topics as necessary
Meet at least annually with the PSI Advisory Committee and the NIGMS staff to discuss progress of the PSI network in reaching the goals set by the NIGMS/NIH staff and Councils and in meeting the needs of the scientific community
Prepare annual reports on progress in meeting milestones and goals of the PSI and publicize progress through the PSI-Structural Genomics Knowledgebase and other appropriate venues for publication
Develop procedures and policies for PSI:Biology network activities, including laboratory information management systems, data management and deposition, publications, reports, etc. for consideration by the PSI Advisory Committee and the NIGMS Council
Communicate with the scientific community on scientific and technological achievements of the network

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

PSI Advisory Committee

The PSI Advisory Committee is a working group of the NIGMS Advisory Council. It will advise NIH staff and the Council on the management, progress, and plans for the PSI:Biology initiative. The membership will be appointed by the PSI:Biology Network Director, following consultation with the Director of NIGMS. Members will include at least one NIGMS Advisory Council member, plus additional consultants as deemed necessary to provide appropriate guidance to the NIGMS Advisory Council.

This PSI Advisory Committee will:

Attend the annual PSI meeting
Meet at least once a year with the Steering Committee and NIH staff prior to the submission of the annual PSI progress report to the NIGMS Advisory Council
Examine and comment on target selection policy and progress toward milestones
Review and comment upon the biological impact of both structural and functional studies completed by the network
Provide advice to the Principal Investigators and Steering Committee about meeting the PSI goals and plans for future directions
Raise issues for consideration by the Principal Investigator and the Steering Committee
Review progress of the Knowledgebase specifically in its annual report to the NIGMS Advisory Council
Comment on the appropriateness of the level of NIGMS support to achieve the goals of the project.

Goals and Milestones

Appropriate goals and annual milestones for each of the components of the PSI:Biology network will be set to ensure that the overall goals of the initiative are met. Initial milestones will be determined by negotiation between the applicant and the NIH Program Director assigned to the Knowledgebase during the award process and will be included in the Terms and Conditions of Award. Milestones will be further refined as the PSI:Biology initiative evolves with input from the Steering Committee and PSI Advisory Committee and renegotiated annually as part of the non-competing continuation award process. The NIH may reduce or withhold funds for failure to meet milestones agreed upon by the investigators and NIH staff.

Reports

The PSI:Biology Network Steering Committee will produce an annual report on the progress made toward the annual goals and milestones. The report will be delivered to the NIGMS staff and PSI Advisory Committee within one month of the annual meeting.

Data Sharing Policies

The PSI:Biology network will be governed by the Data Sharing Policies that have governed PSI-1 and PSI-2. Coordinates of solved structures, along with structure factors, MUST be deposited in the Protein Databank within four weeks of completing the refinement of the structure. Data must be released by the PDB to the public immediately, unless the dataset is designated as a "technology development data set" to be used in CASP-like tests of software development. In any event, ALL structural data must be made public within eight weeks. In addition, protein targets adopted by the High-Throughput Structure Determination centers must be entered in the TargetDB, including those arising from the Consortia for High-Throughput-Enabled Structural Biology Partnerships and those submitted through the community nominations process. Furthermore, progress on these targets must be updated on a monthly basis. As work progresses, appropriate data must be entered in the PepcDB regarding the methods and success or failure of various steps in the structure determination pipeline in a timely fashion. Finally, all components of the PSI must abide by all NIH policies for sharing of published information through PubMedCentral and must also abide by policies of the PSI:Biology network requiring the deposition of information about publications and other activities in the PSI-Structural Genomics Knowledgebase. Participants must also contribute appropriate information to the PSI Investigators Intranet website as necessary to facilitate communication between the various components of the PSI.

PSI:Biology Resource Sharing Policies

All funded components of the PSI:Biology network are expected to deposit vectors and clones developed with PSI:Biology funding or used in PSI:Biology research into the PSI-Materials Repository. The Knowledgebase must link to the PSI-Materials Repository in ways that facilitate the dissemination of information about resources generated by the PSI:Biology network.

Intellectual Property Policies

Normal NIH guidelines regarding intellectual property will apply to these awards. However, it is expected that the above data sharing and experimental resource sharing activities will take place in a timely fashion, even if IP protection activities are delayed.

2.A.4. Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's rights in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

In addition to the Non-Competing Continuation Award Progress Report (PHS 2590) and reports on the operation of the overall PSI:Biology network to be produced by the PSI:Biology Network Steering Committee and the PSI Advisory Committee, each Principal Investigator will be required to submit annual highlights of progress that will be shared with other members of the PSI:Biology network via the Knowledgebase. These reports will be in the form of text documents (or PDF files) with figures, tables, and formats to be determined by the Principal Investigator. The reports are intended to facilitate coordination of effort and sharing of methodological advances.

The Knowledgebase Director will be required to report progress to the PSI:Biology Research Network Steering Committee at its annual meetings and at more frequent intervals (not to exceed monthly reports) as determined by the Steering Committee. Progress of the Knowledgebase will be reviewed annually by the PSI:Biology Advisory Committee and the NIGMS PSI:Biology Network Director and reported to the National Advisory General Medical Sciences Council.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Peter C. Preusch, Ph.D.
Cell Biology and Biophysics Division
National Institute of General Medical Sciences
Building 45, Room 2As-13C
45 Center Drive
Bethesda, MD 20892
Telephone: (301) 594-1158
FAX: (301) 480-2004
Email: preuschp@nigms.nih.gov

2. Peer Review Contacts:

Helen R. Sunshine, Ph.D.
Office of Scientific Review
National Institute of General Medical Sciences, NIH
45 Center Drive, Room 3An.12F, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-2881
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov

3. Financial or Grants Management Contacts:

Earl C. Melvin
Division of Extramural Activities
National Institute of General Medical Sciences
45 Center Drive, Room 2An.32E, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-3912
FAX: (301) 480-2554
Email: melvine@nigms.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (https://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (https://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see https://grants.nih.gov/grants/gwas/

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see https://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement https://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (https://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at https://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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