Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of General Medical Sciences (NIGMS)

Funding Opportunity Title

High-Throughput-Enabled Structural Biology Partnerships (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of PAR-10-214

Related Notices
  • February 9, 2012 - This Notice is to inform prospective applicants that NIGMS will terminate Funding Opportunity Announcement (FOA) PAR-11-176 effective May 9, 2012. See NOT-GM-12-101.
  • April 29, 2011 - Clarification of Instructions for PAR-11-176, Section IV part 2, "Content and Form of Application Submission" . See NOT-GM-11-107.
Funding Opportunity Announcement (FOA) Number

PAR-11-176

Companion FOA

None

Number of Applications

See  Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.859

FOA Purpose

This FOA encourages applications to establish partnerships between researchers interested in a biological problem of significant scope and researchers providing high-throughput structure determination capabilities through the NIGMS PSI:Biology network.  Applicants to this FOA should propose work to solve a substantial biological problem for which the determination of many protein structures is necessary.  The proteins should be amenable to high-throughput structure determination and/or should provide suitable targets to motivate new technology development.  Awardee principal investigators 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.

Key Dates
Posted Date

March 24, 2011

Open Date (Earliest Submission Date)

May 5, 2011

Letter of Intent Due Date

Letters of Intent should be submitted 30 days before the anticipated receipt date.

Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization.

Scientific Merit Review

Standard dates apply

Advisory Council Review

Standard dates apply

Earliest Start Date(s)

Standard dates apply

Expiration Date

May 9, 2012 per NOT-GM-12-101 (Previously September 8, 2014)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This FOA encourages applications to establish partnerships between researchers interested in a biological problem of significant scope and researchers providing high-throughput structure determination capabilities through the NIGMS PSI:Biology network.  Applicants should propose work to solve a substantial biological problem for which the determination of many protein structures is necessary. The proteins should be amenable to high-throughput structure determination or should provide suitable targets to motivate new technology development.  The proteins generally should be of unknown structure and preferably likely to be of novel structure.  Ideally, the solution of these protein structures will also contribute to the understanding of protein sequence-structure relationships in general.  The project should involve both studies of protein function by the applicant researchers and structural studies by the PSI:Biology network.  Projects may focus on proteins that are the subject of other grant applications, but the specific aims must clearly differ, both with respect to functional studies to be conducted and with respect to the goal of structure determination.

It is expected that these awards will lead to new collaborations between researchers emphasizing biological function and researchers emphasizing biological structure. It is expected that the results from these collaborations will contribute to understanding many basic and biomedically important research problems as well as to our fundamental understanding of protein structure.  Example areas of interest are discussed below.

Background

This FOA is part of a new NIGMS initiative, PSI:Biology [http://www.nigms.nih.gov/Initiatives/PSI/Biology/], that is being established through a series of RFAs (Request for Applications) and PARs (program announcements with ongoing 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 Protein Structure Initiative (PSI).  The PSI was initiated in FY2000, after extensive dialog with the scientific community, with the ultimate goal of significantly advancing the understanding of 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 which 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 http://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.

In 2008, the PSI Advisory Committee 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 (PAs), 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 PAs. Based on these recommendations, NIGMS staff presented a Concept Clearance document to the NIGMS Council at its January 2009 meeting, and the Council approved those plans, which are being implemented (see RFA-GM-10-005, RFA-GM-10-006 and RFA-GM-10-007).  This PAR represents an on-going opportunity to apply for the program that was described more extensively in RFA-GM-10-007 Consortia for High-Throughput-Enabled Structural Biology Partnerships.

Objectives of this FOA

This FOA encourages applications for High-Throughput-Enabled Structural Biology Research projects.  These projects will provide the biological problems that will drive the PSI:Biology initiative.  The high-throughput centers to be funded primarily through RFA-GM-10-005 will focus up to 70% of their effort on solving structures of targets that are to be determined through the Consortia for High-Throughput-Enabled Structural Biology Partnerships (RFA-GM-10-007), the High-Throughput-Enabled Structural Biology Research projects (PAR-11-176, i.e., this FOA), and through other modes of community nomination of targets.  The centers for membrane protein structure determination funded primarily through RFA-GM-10-006 will focus up to 30% of their effort on similarly identified collaborative and community nominated targets.  Applicants for this FOA define the general area of science to be studied and the specific proteins for which structures are to be determined.  The results should be of interest to a significant number and/or a broad range of scientists.  The proteins should be of unknown structure, rather than minor variations on proteins of known structure, e.g., mutations or different bound ligands.  Exceptions may be made in compelling cases.  Sequence novelty and predicted structural uniqueness of the target proteins is secondary to the importance of understanding their biological function, but is a significant other consideration and is to be assessed as described below under Application Procedures.  Protein targets should ideally contribute to coverage of protein sequence, family, and fold space and should provide as much leverage of additional sequence space as possible.  Assistance in evaluating this aspect of proposed protein targets is available through the Sequence Comparison and Analysis tool [http://cnt.sbkb.org/CNT/targetlogin.jsp] module of the PSI StructuralBiology Knowledgebase as described under  Section IV."  Sources may be either prokaryotic or eukaryotic.  In some cases, only the structure of the exact protein from a specific organism will suffice; however, the odds of success will improve if related proteins of the same family or of other organisms can also provide the needed structural information to generate an adequate model for the target.  Protein targets should be amenable to high-throughput approaches or should drive technology development by the PSI:Biology network centers.  Intermediate products of the structure determination pipeline (clones, proteins, procedures) between gene sequence and structure solution should be of value, even if the structure is not solved.  These intermediate products must be deposited in the PSI-Materials Repository and the PSI-Structural Genomics Knowledgebase, or otherwise shared with the broad scientific community.

In addition to specifying targets to be solved, the biological partnerships will provide the linkage between structure and function by proposing and conducting studies that will contribute to understanding the biological function of the proteins and their structure-function relationships.  This work may involve utilization of results and resources generated by the PSI:Biology network beyond the solved structures, e.g., the proposed work may utilize vectors, clones, reagents, models and other resources generated by the network.  Targets proposed by the partners may drive technology development for structure determination, informatics, and model generation that will be carried out jointly with the PSI:Biology network.  Partnerships might also develop ideas about protein structure based on the database of solved PSI structures (and others); e.g., evolution of protein families and fundamental protein structure motifs.  The partnerships will ensure the biological impact of the solved structures by facilitating the interpretation of structural results, putting the structural studies in their biological context, and actively contributing to dissemination of PSI:Biology results.  As partners, both applicants and the PSI:Biology network should have a stake in the outcome of the research.  The PSI:Biology network is not intended to provide simply a structure determination service.  The partnerships will establish consortium arrangements with one or more of the PSI:Biology network centers to be established during the initial year of the award.

Projects that are amenable to high-throughput structure determination will likely have the following general requirements:

The following specific areas of scientific opportunity were identified during the Future Structural Genomics Initiatives meeting.  Please see the meeting report for additional description:

The above list should not be considered to be comprehensive.  Applications proposing research outside the above areas but still appropriate to the goals of PSI:Biology are welcome.

PSI:Biology Network Operations and Governance

All awarded components of the PSI:Biology initiative 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 "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.

After initiation of the PSI:Biology network, the Steering Committee and the PSI Advisory Committee (see immediately below) will meet jointly with NIH staff to determine how to best carry out the overall distribution of targets throughout the network, including those proposed by the funded Consortia for High-Throughput-Enabled Structural Biology Partnerships.  Further refinement of target distribution plans will be carried out by these same groups on a regular basis throughout the lifetime of the initiative.  Partnership representatives will participate in all discussions of target distribution and network capacity allocation, along with representatives of the high-throughput and membrane protein structure determination centers.

Each center will be expected to abide by the decisions of the Steering Committee and to provide due diligence in the pursuit of their assigned targets.  Functional study design and execution funded by the U01 awards will be the responsibility of the awardees with minimal input from the Steering Committee, but it is expected that a collegial collaborative relationship will be developed with structure determination center investigators working specifically on the awardee’s targets.

External Input to the Network

The PSI Advisory Committee will provide external input to the PSI:Biology Network Steering Committee and to NIH staff.  Individual components of the network may have their own External Advisory Committees, if the scope of the component warrants such a committee.

Commitment to Diversity

Reports from the National Science Foundation (e.g., Broadening Participation at the National Science Foundation: A Framework for Action, August, 2008) and the National Academy of Sciences (e.g., Advancing the Nation’s Health Needs: NIH Research Training Programs,  National Research Council,  Washington, DC. National Academy Press, 2005) emphasize the need for a well-trained diverse scientific workforce. The NIH recognizes a unique and compelling need to promote diversity in the biomedical, behavioral, clinical and social sciences workforce. The NIH expects efforts to diversify the workforce to lead to the recruitment of the most talented researchers from all groups; to improve the quality of the educational and training environment; to balance and broaden the perspective in setting research priorities; to improve the ability to recruit subjects from diverse backgrounds into clinical research protocols; and to improve the Nation’s capacity to address and eliminate health disparities.  The NIGMS is committed to promoting and advancing the diversity of its biomedical scientific workforce.  See:  http://www.nigms.nih.gov/News/Reports/workforcediversity_100307.htm.   

Accordingly the NIH continues to encourage institutions to diversify their student and faculty populations and thus to increase the participation of individuals currently underrepresented in the biomedical, clinical, behavioral, and social sciences such as: individuals from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from socially, culturally, economically, or educationally disadvantaged backgrounds that have inhibited their ability to pursue a career in health-related research. Institutions are encouraged to identify candidates who will increase diversity on a national or institutional basis. 

The NIH is particularly interested in encouraging the recruitment and retention of the following classes of candidates:

A.  Individuals from racial and ethnic groups that have been shown by the National Science Foundation to be underrepresented in health-related sciences on a national basis (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the report Women, Minorities, and Persons with Disabilities in Science and Engineering, 2007, p. 262).   The following racial and ethnic groups have been shown to be underrepresented in biomedical research: African Americans or Blacks, Hispanic Americans or Latinos, American Indians or Alaska Natives, Native Hawaiians or other Pacific Islanders.  In addition, it is recognized that under-representation can vary from setting to setting and individuals from racial or ethnic groups that can be convincingly demonstrated to be underrepresented by the grantee institution should be included in the Recruitment and Retention Plan to Enhance Researcher Diversity (see below, Section IV.2).

B.  Individuals with disabilities, who are defined as those with a physical or mental impairment that substantially limits one or more major life activities.

C. Individuals from disadvantaged backgrounds who are defined as:

1. Individuals who come from a family with an annual income below established low-income thresholds.  These thresholds are based on family size, published by the U.S. Bureau of the Census; adjusted annually for changes in the Consumer Price Index; and adjusted by the Secretary for use in all health professions programs.   The Secretary periodically publishes these income levels at http://aspe.hhs.gov/poverty/index.shtml.   For individuals from low income backgrounds, the institution must be able to demonstrate that such candidates (a) have qualified for Federal disadvantaged assistance; or (b) have received any of the following student loans: Health Professional Student Loans (HPSL), Loans for Disadvantaged Student Program; or have received scholarships from the U.S. Department of Health and Human Services under the Scholarship for Individuals with Exceptional Financial Need.

2. Individuals who come from a social, cultural, or educational environment such as that found in certain rural or inner-city environments that have demonstrably and recently directly inhibited the individual from obtaining the knowledge, skills, and abilities necessary to develop and participate in a research career.

Recruitment and retention plans related to a disadvantaged background are most applicable to high school and perhaps undergraduate candidates, but would be more difficult to justify for individuals beyond that level of achievement.

In order to promote an NIGMS-supported biomedical workforce that is diverse, applicants responding to this initiative must propose creative ways to enhance and/or successful ways to ensure diversity on their research teams. 

The PSI:Biology research groups should reflect the commitment of the NIH and NIGMS to enhance the diversity of the scientific workforce and applications should include recruitment and retention plans to enhance researcher diversity.

Sharing of Data and Material Resources under this Initiative

A central feature of the PSI:Biology initiative is the timely deposition and sharing of data through the PSI-Structural Genomics Knowledgebase, and timely sharing of research resources through depositions to the PSI-Materials Repository and by other mechanisms.  Details of these requirements are described under the "Cooperative Agreement Terms and Conditions of Award" that are discussed in Section VI.2 "Award Administration Information".

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal
Resubmission

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

The expected budget range is from $250,000 to $1.5 million direct costs (up to $2.5 million total costs) per year for project periods of 2-4 years.  

Award Project Period

Scope of the proposed project should determine the project period. The maximum period is 4 years. 

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. However, such institutions may be included as part of consortium applications submitted by any other type of eligible institution.

Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her 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.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.  

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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.

By the date listed in Part 1. Overview Information, 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 PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Ward W. Smith, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences (NIGMS)
45 Center Drive, MSC 6200
Building 45, Room Number 2AS.19F
Bethesda, MD 20892
Telephone: 301-443-9375
Email: smithwar@nigms.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed..

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims

Applicants should succinctly state the scientific objectives of the PSI:Biology research project and should clearly delineate what work is to be done by the applicants and what is to be done by the PSI:Biology network centers.

Research Strategy 

Under significance, the applicants should provide a strong biological and/or biomedical motivation for the proposed studies.  This should include information about the significance of the overall problem and of the particular contribution that determining the proposed structures will make to understanding or progress in the field.  This section should also explain how the work to be done by the investigators will integrate with the work to be carried out by the PSI:Biology network Centers for High-Throughput Structure Determination and/or Centers for Membrane Protein Structure Determination.  For example, who will be responsible for protein production, which experiments will be performed at which sites, how experiments on function will be informed by structural results.

Under Approach, applicants should describe in detail how the work is to be conducted.  This should include detailed plans for work to be conducted in the applicants' laboratories.  Work to be conducted by the PSI:Biology network centers may be described in more schematic form but should demonstrate an understanding of the general capabilities and challenges of high-throughput structural biology.

Applicants should include as preliminary studies any analysis that they have carried out with respect to the sequence and structure space coverage/leverage of their proposed targets.  For example, this material should include information about the solved structures of the nearest known family or superfamily members (percent homology of proposed targets to nearest neighbors).  It should include information about the likely leverage that a solved structure would provide for the modeling of other proteins of unknown structure.  This type of information is available through the PSI StructuralBiology Knowledgebase and it is highly recommended that applicants subject their proposed target sequences to the analysis available there through the Sequence Comparison and Analysis tool (http://cnt.sbkb.org/CNT/targetlogin.jsp).  The results should be presented in an appendix to the application.  Similarly, applicants should search the PSI-Materials Repository to determine which plasmids relevant to their project have already been deposited and include plans to make use of such materials.  This material should also be included in the appendix. Other preliminary results, including preliminary studies on biological function, may be included as the investigators wish.  In the case of investigators who have collaborations with currently funded PSI Centers they should highlight any preliminary results from these collaborations.

Budget

This FOA uses non-modular budget formats. A single overall project budget should be presented on form page 4 and a budget for the entire proposed period of support on form page 5.  Subproject budgets are not allowed.  Consortium budgets should be included as necessary.  Consortium subcontract indirect costs (Facilities and Administration, including F&A costs required to set up and maintain subcontracts) do not count against the upper direct cost budgetary limits for this announcement; however, they will count against the overall total cost limit of $2.5 million.

The budget should include personnel, consultant costs, equipment, supplies, and other expenses costs that will support work to be performed in the applicants' laboratories.  The budget should include under Other Expenses funds that are expected to support the determination of structures by the PSI:Biology network centers.  No more than one-half of the total direct costs budget should be designated for this purpose.  The estimated cost per structure depends on the nature of the protein target and the probability that it will be amenable to high-throughput structure determination.  The current cost for solution of soluble protein targets by PSI-2 is close to $50,000.  However, since a large part of the costs for structure determination will be awarded to the centers through RFA-GM-10-005, use an estimate of $10,000 per structure when preparing the budget.  For more difficult protein targets (e.g., membrane proteins and complexes) higher figures should be used and the estimates justified.  These structure determination funds will not be awarded by the NIH until the grantee, in consultation with the PSI:Biology Steering Committee, has identified the specific PSI:Biology high-throughput centers and/or membrane protein centers with which the grantee investigators will be working.  Once these consortium arrangements are in place, NIH will provide funds to the parent award to support the required subawards.  For planning purposes, estimate subaward F&A costs at 50%.  Actual subaward F&A costs will be recalculated once the consortium institutions have been identified.

Applicants should plan for and may request funds to support the travel of the principal investigators and one or more other scientific staff members to attend at least two PSI:Biology initiative meetings of up to two days each per year.  This is in addition to requesting travel funds for normal attendance at scientific meetings.

Applicants should request funds to support an annual meeting of all partnership investigators and also funds to support travel expenses and consultant costs of an Annual External Advisory Committee meeting, if the scope of the project warrants these activities.

Applicants should request funds to support any special activities proposed under the Plan for Data Sharing and Dissemination and the Plan for Sharing Material Resources.

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" that are discussed in Section VI.2 "Award Administration Information" and applicants 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 applicants' laboratories and those of the PSI:Biology network.  Depending on the scope of the project, it may be appropriate to plan for 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.  Similarly depending on scope, it may be appropriate to plan an annual meeting to bring all participating investigators together at least annually.  Means for more frequent communication should also be described.

Recruitment and Retention Plan

Applicants must propose ways to reflect the NIH and NIGMS commitment to enhancing the diversity of the scientific workforce.  Applicants should provide information on the diversity of the proposed research teams and plans to enhance and/or ensure the continued diversity of their research teams.  This section of the application will not be considered by the peer review group, but will be considered by NIH staff as part of the award process.

Intellectual Property Statement

An institution's stance must be consistent with the goals of advancing and not hindering future research.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide. with the following modifications:

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modifications:

Some materials other than publications that are related to NIGMS High-Throughput-Enabled Structural Biology Partnership applications (but not typically included in research grant applications) may be included as appendices.  The appendix may be used to provide materials that are too cumbersome to include in the Research Strategy sections without disrupting the narrative flow. These appendix items provide material related to the research, and are not scored by the reviewers. The following should be included as PDF files:

·         The output from searching the PSI-Biology Knowledgebase Target Analysis module for data on the relationship of proposed targets to already proposed targets and known structures.

·         The output from searching the PSI-Materials Repository for previously deposited plasmids relevant to the proposed research.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

4. Intergovernmental Review (E.O. 12372)

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.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.  

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed. .

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115. .

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of 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 review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific 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?  Does the proposed problem make appropriate use of the capabilities of the PSI:Biology network centers for structure determination?  Will the solution of the proposed structures by the PSI:Biology network centers contribute to solving a biologically important problem?  Will the solved structures contribute to the secondary goal of determining novel protein structures and increasing the coverage of sequence/structure space?  Do the proposed targets pose challenges that will stimulate technology development?  Does the work to be conducted in the applicant investigators' laboratories make a significant contribution to solving the biological problem?

Investigator(s)    

Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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? Do the investigators demonstrate the potential to be interactive and effective members of the PSI:Biology network?  Do the partners provide capabilities for functional characterization of proteins that complement the structural capabilities of the centers?  For applications involving more than one investigator, is there evidence of synergy among the members of the partnership or the potential for such synergy to develop?  Do(es) the PD/PIs 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?  Does the partnership bring together collaborations between researchers in ways that will lead to new scientific insights? 

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?  

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 evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Management Plan: 

Is an adequate plan presented to assure the productive and collaborative management of the project and interactions with other components of the PSI:Biology network?

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. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

 For Renewals, the committee will consider the progress made in the last funding period.

Revisions

 Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

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).

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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NGMS , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Advisory General Medical Sciences Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.      

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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.

The PD(s)/PI(s) will have the primary responsibility for:

Awardees 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.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The PSI:Biology Network Director will have the responsibility for:

NIH staff serving as scientific liaisons will have the responsibility for:

NIH staff serving as program directors will have the primary responsibility for:

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.

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

Areas of Joint responsibility include:

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.  In the case of awards involving Multiple PD(s)/PI(s), each PSI:Biology component will be entitled to one voting member.  The NIGMS/NIH Scientific Liaisons and the PSI:Biology Network Director 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 leaders 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 PSI:Biology Network Steering Committee will have the primary responsibility to:

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.

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.

The PSI  Advisory Committee will have the primary responsibility to:

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 application during the award process and will be included in the Terms and Conditions of Award. Scientific Liaisons may assist the PD(s)/PI(s) in setting milestones, but do not have authority to approve them.  This authority rests with the NIH Program Director. 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.

PSI:Biolgoy 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.

PSI:Biology Data Sharing:

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 of the PSI:Biology network (including those of the partnerships) must be entered in the TargetDB upon assignment to any PSI:Biology network structure determination component.  Furthermore, progress on these targets must be updated on a monthly basis by either the component to which the structure determination has been assigned or by the partnership that has proposed the target for structure determination.  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:

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.

PSI:Biology Intellectual Property:

Normal NIH guidelines regarding intellectual property will apply to these grants.  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.

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 Dispute Resolution. 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 right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16..

3. Reporting

When multiple years are involved, 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.

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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Potential applicants are strongly encouraged to contact NIGMS staff to discuss the research strategy before submitting an application.

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Ward W. Smith, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences (NIGMS)
45 Center Drive, MSC 6200
Building 45, Room Number 2AS.19F
Bethesda, MD 20892
Telephone: 301-443-9375
FAX: 301-480-2004
Email: smithwar@nigms.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Earl C. Melvin
Grants Administration Branch
Division of Extramural Research
National Institute of General Medical Sciences  (NIGMS)
45 Center Drive, MSC 6200
Building 45, Room Number 2AN.32E
Bethesda, MD 20892
Telephone: (301) 594-3912
FAX: 301-480-2554
Email: melvine@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

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 Part 52 and 45 CFR Parts 74 and 92.


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