Part I Overview Information

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Department of Health and Human Services

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

Components of Participating Organizations
THIS RFA IS DEVELOPED AS A ROADMAP INITIATIVE.   ALL NIH INSTITUTES AND CENTERS PARTICIPATE IN ROADMAP INITIATIVES.  This RFA will be administered by the National Institute of General Medical Sciences on behalf of the NIH, (http://www.nigms.nih.gov).

Title: Centers for Innovation in Membrane Protein Production for Structure Determination (P50)

Announcement Type
This is a reissue of RFA-RM-04-009.

Request For Applications (RFA) Number: RFA-RM-08-019

Catalog of Federal Domestic Assistance Number(s)
93.310

Key Dates
Release Date:  June 13, 2008
Letters of Intent Receipt Date: September 21, 2008
Application Receipt Date: October 21, 2008
Peer Review Date: February/March 2009
Council Review Date: May 2009
Earliest Anticipated Start Date: August 1, 2009
Additional Information To Be Available Date (Url Activation Date): Not applicable.
Expiration Date: October 22, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose.  The goal of the Centers will be the development of innovative tools and methods to produce functional membrane proteins for structural studies.  Centers should involve multiple, diverse, and cooperating investigators who bring together innovative combinations of scientific disciplines.  The Centers will disseminate their results, methods, and materials in a timely manner and establish broad-based collaborations and community training.  They will also track state-of-the-art developments in membrane protein production and structure determination and serve as networking centers for the entire Structural Biology Roadmap initiative.  The activities of these Centers should complement the activities of investigator-initiated research, as supported by the R01 grant mechanism.

This FOA solicits applications for Centers for Innovation in Membrane Protein Production for Structure Determination.  The goals of these Centers will be to create enabling technologies and to focus on innovative, high-impact, and multidisciplinary approaches to sample preparation of structurally and functionally intact membrane proteins for structural determination.  The collaborative and coordinated effort made possible by multidisciplinary investigators associated with such Centers is required to accelerate technological advances in obtaining the high-resolution structure of membrane proteins.

• Mechanism of Support. This FOA will utilize the P50 Specialized Center Grant award mechanism to promote multidisciplinary research.
• Funds Available and Anticipated Number of Awards. The total amount of funding that the NIH Roadmap expects to award through this announcement is $5 million in FY09; the anticipated number of awards is 2-3 Centers.  
• Budget and Project Period.  The total project period for an application submitted in response to this funding opportunity may not exceed five years.  Direct costs are limited to no more than $1.5 million for the first year.
• Application Research Plan Component Length: This P50 application Research Plan component of the PHS398 (Items 2-5) may not exceed 60 pages, including tables, graphs, figures, diagrams, and charts. https://grants.nih.gov/grants/funding/funding_program.htm
• 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 PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions.  Resubmission applications are not permitted in response to this FOA. 
• Renewals.  The two currently funded Roadmap Centers for Innovation in Membrane Protein Production may submit renewal applications 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

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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 and Information

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
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

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Section I. Funding Opportunity Description

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1. Research Objectives

This FOA solicits applications for Centers for Innovation in Membrane Protein Production for Structure Determination.  The goals of these Centers will be to create enabling technologies and to focus on innovative, high-impact, and multidisciplinary approaches to sample preparation of structurally and functionally intact membrane proteins for structural determination.  The collaborative and coordinated effort made possible by multidisciplinary investigators associated with such Centers is required to accelerate technological advances in this important area. 

Background

Membrane proteins play a crucial role in many cellular and physiological processes.  They are essential mediators of material and information transfer between cells and their environment, between compartments within cells, and between compartments comprising the organ systems.  Functionally normal membrane proteins are vital to health, and specific defects are associated with many known disease states.  Membrane proteins are the targets of a large number of pharmacologically and toxicologically active substances and are responsible, in part, for their uptake, metabolism, and clearance.

Considerable research is ongoing in the area of membrane protein structure and function, yet relatively few investigators have applied the techniques of x-ray crystallography, electron diffraction, or NMR spectroscopy to study directly the structures of their proteins.  During the past two decades, approximately 150 unique membrane protein structures have been solved, and each structure has been a major contribution in its area of science.   (See http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html  and/or http://www.mpibp-frankfurt.mpg.de/michel/public/memprotstruct.html). This progress clearly demonstrates that obtaining membrane protein structures is feasible.  However, during these same decades, the rate of soluble protein structure determination has accelerated greatly, and there remains a gap between the understanding of membrane proteins and their soluble protein counterparts (1).

During the past ten years, NIH has stimulated work on membrane protein structures through a series of program announcements (2).  This approach has been partially successful and additional NIH funding of this area has resulted.  However, certain types of essential technology development and non-hypothesis-driven research have been only modestly supported.  Until recently, specific funds have not been set aside for work on membrane proteins. 

An increase in the number of known membrane protein structures will contribute to an enhanced understanding of many basic phenomena underlying cellular functions essential to human health.  To address this and other difficult research problems, the NIH Director, Dr. Elias Zerhouni established the NIH Roadmap process for program initiative prioritization in 2003 (http://nihroadmap.nih.gov/).  This process identified Structural Biology, especially the determination of membrane protein structures, as a major area for additional investment.

The Structural Biology Roadmap process has been critical in creating a specific set-aside of funds dedicated to the production of membrane protein for structural studies.  As a result, an FOA was issued in FY04 that solicited applications to establish Centers for Innovation in Membrane Protein Production (3) and two Centers were funded in late FY2004.  A follow-on solicitation for R01, P01, and R21 applications was issued in FY2005 (4).  Funds committed to R21 Roadmap applications funded in FY2005 became available for re-competition in FY2007 so an RFA for three-year R01 applications was issued in FY2007 to continue development in the targeted areas of science (5). 

The last two solicitations were intended to complement the Centers and to encourage novel investigator-initiated ideas through smaller scale activities such as exploratory studies for high-risk research, regular research projects, and program projects.  Furthermore, although production of protein is a key limiting step in the solution of membrane protein structures, it is not the only problematic step.  Therefore, these two RFA were broadened to include all activities necessary to produce high-resolution structural models of membrane proteins.  Applications funded in response to all three FOAs in the first phase are listed on the Roadmap web site (6): http://nihroadmap.nih.gov/grants/fundedresearch.asp . 

In a recent Mid-Course Review in January 2008, the panel members were extremely enthusiastic about the goals, accomplishments, and impact of the Centers for Innovation in Membrane Protein Production.  They recommended continuation of these Centers and more emphasis on dissemination of results and on community training.  The Mid-Course Review Panel was also enthusiastic about the crucial and complementary contributions of the investigator-initiated projects.  The Executive Summary of the Mid-Course Review is posted on the Roadmap website.  Based in part on this review, the Structural Biology Roadmap initiative has been approved for continued funding of a combination of Centers (P50) and research projects (R01).  This RFA solicits proposals for Centers to be funded in FY2009.  An FOA is expected to be released next year for funding of R01 projects to be funded in FY2010.

Scientific Objectives

The second phase of the Structural Biology Roadmap will continue to focus on the development of innovative, systematic and coordinated approaches to the production of membrane proteins in functionally relevant forms for structure determination.  The goals are to develop approaches that will make the solution of simple membrane protein structures routinely achievable and novel methods that can be applied to more complicated membrane proteins containing multiple subunits of the same (homo-oligomers) and different (hetero-oligomers) structure.  Another goal is to produce and determine structures for complexes that are formed between membrane proteins and their soluble protein partners, small ligands and/or macromolecules.

The scientific goal of the Centers, not possible with other funding mechanisms or previous program announcements, will be the non-hypothesis-driven development of innovative tools and methods for the expression, solubilization, stabilization, reconstitution, and purification of membrane proteins for structural studies.  In addition to encouraging the development of new methods, this FOA also seeks to support new efforts to accomplish the solution of membrane protein structures at atomic resolution through the application of current state-of-the-art methods.

It is expected that many of the projects will be collaborative efforts between chemists, biochemists, molecular biologists, and biophysicists with expertise in the synthesis of probes, novel solubilizing and stabilizing reagents; in cloning and expression; in the isolation and characterization of integral membrane proteins; and in x-ray crystallography, NMR, and other structural methods.  A major aim of this FOA is to stimulate such multidisciplinary collaborations. 

Targeted areas of research for the Centers may include, but are not limited to:

• Innovative methods that will yield structurally and functionally intact membrane proteins for subsequent structural studies.  Thus far, most membrane protein structures have been solved for proteins that can be obtained from naturally rich sources.  However, many of the proteins of greatest human physiological and pharmaceutical relevance are of relatively low abundance.  Although membrane proteins may be expressed in recombinant form, there is a need to develop more robust expression systems. 
• Efficient co-expression of membrane protein subunits and assembly systems for production of functional hetero-oligomeric integral membrane proteins and complexes suitable for structural studies.  Studies designed to advance the production and determination of the structures of functional protein complexes involving intrinsic membrane proteins and their interacting membrane-bound or non-membrane protein partners are also needed.
• Insights into the ways that detergents and lipids interact with membrane proteins.  For example, it is not clear why certain detergents and/or lipids with novel phase properties are more successful in the solubilization of membrane proteins than others.  Innovations are needed in the chemical synthesis of novel detergents and/or the development of non-detergent methods for solubilizing and stabilizing membrane proteins.  Efficient methods are needed to characterize the functional state of the expressed and purified membrane proteins as well as their lipid and detergent contents, state of aggregation, physical homogeneity, and sequence microheterogeneity.
• Innovations in the fractionation and purification of membrane proteins.  Novel applications of genomic and proteomic approaches and screens that might complement or enhance traditional approaches such as centrifugation, partitioning, precipitation, chromatography, isoelectric focusing, and electrophoresis are requested.  Non-traditional approaches such as the use of protein and/or lipid chaperones, conformation-specific antibodies, covalent modification, stabilizing mutations, and structural scaffolds could be developed to express, solubilize, and purify membrane proteins. 
• Innovative methods for x-ray crystallography of membrane proteins.  These may include novel apparatus and reagents for membrane protein crystallization as well as efforts to improve the crystallizability of the target protein such as sequence modifications, fusion proteins, antibody complexes, and other co-crystallization aids.  Additional innovations are needed to stabilize, freeze, and manipulate often fragile membrane protein crystals for data collection.  Given the large size of many membrane proteins and often lower quality diffraction, phasing can be difficult; new approaches are needed here as well.  Finally, insights gained through analysis of the structures of membrane proteins and their crystallization habits may be useful.
• Developments that would significantly improve the ultimate resolution of single particle electron microscopic and electron diffraction methods applied to 2D and other crystal forms to atomic resolution and improve their general applicability to membrane proteins.
• Innovations in both solid state and solution NMR spectroscopy methods to improve their applicability to larger size membrane proteins.  Improvements are needed in isotopic labeling methods and for data collection on limited samples with significant non-protein background signals from detergent and lipids.
• Innovations in other biophysical techniques, such as mass spectrometric methods, that can yield substantially detailed information about overall membrane protein structure leading to models comparable in quality to those of x-ray and NMR methods.  Innovative, sensitive mass spectrometric methods are needed to characterize the homogeneity and stoichiometry of membrane protein assemblies, relating functionality to required constituents.

Training and Workforce Diversity Objectives

Centers are expected to play a major role in training new scientists in the determination of membrane protein structures.  Center investigators are encouraged to recruit and mentor students and postdoctoral trainees, especially members of under-represented minorities, disabled, or disadvantaged groups, in this challenging area of research.

Outreach and Community Development Objectives

The Centers will disseminate their results, methods, and materials in a timely manner by a variety of means such as databases or websites, training workshops, reviews and publications.  They will also track state-of-the-art developments in membrane protein production and structure determination as guides in the selection of appropriate subprojects, cores, approaches, and targets.  The activities of the Centers should complement the activities of investigator-initiated research, as supported by the R01 grant mechanism, and provide networking opportunities that benefit the entire Structural Biology Roadmap effort.  Centers involving multiple, diverse, and cooperating institutions which bring together innovative combinations of scientific disciplines will be encouraged.  A further aim is to encourage additional investigators, particularly new investigators, to begin work in this area.

The focus on innovation in protein production and determination of integral membrane protein structures supported by this FOA will complement other efforts underway to understand the structures of all proteins.  A major activity in this regard is the Protein Structure Initiative or PSI (7).  PSI large-scale Centers are expected to solve large numbers of protein structures in a high-throughput fashion, but membrane proteins are not currently amenable to high throughput efforts.  The above mentioned NIH Roadmap Centers for Innovation in Membrane Protein Production for Structure Determination are intended to address part of this problem.  Additional efforts to address this part of the problem are being undertaken by the Specialized Centers for Protein Structure Initiative (8).  These Centers focus on challenging proteins that are not currently amenable to high throughput methods and therefore represent major bottlenecks of the structural genomics pipeline.  The Specialized Centers are expected to develop methods that will lead to the production and structure determination of significant numbers of these proteins, especially in the later years of the project.

All three types of centers (the PSI large-scale centers, the PSI Specialized Centers, and the Centers for Innovation in Membrane Protein Production for Structure Determination) include information and material sharing activities.  They also have mechanisms for providing access to unique facilities and expertise to the broader scientific community.  They are intended to nucleate efforts for the entire field of protein structure.  Investigators may wish to contact the center directors to see how their work could interface with the activity of the centers.

Investigators are reminded that in addition to this FOA, NIH also seeks to support research on membrane protein structure through the Structural Biology of Membrane Proteins Program Announcement PA-07-253.  See: https://grants.nih.gov/grants/guide/pa-files/PA-07-253.html

Eligible small businesses may also wish to consider applying for support through the regular Omnibus Solicitation for the SBIR or STTR program.  See: https://grants.nih.gov/grants/guide/pa-files/PA-07-280.html and  https://grants.nih.gov/grants/guide/pa-files/PA-07-281.html .

References:

(1)  The progress of membrane protein structure determination.  Stephen H. White, Protein Science (2004), 13:1948–1949.

(2)  Structural Biology of Membrane Proteins Program Announcements (PA-95-035, PA-99-004, PA-02-060, PA-06-119) and Structural Biology of Membrane Proteins SBIR/STTR Announcement (PA-02-108).  See NIH Guide:  https://grants.nih.gov/grants/guide/pa-files/

(3)  Centers for Innovation in Membrane Protein Production (P50) (RFA-RM-04-009).  See:http://grants1.nih.gov/grants/guide/rfa-files/RFA-RM-04-009.html.

(4) Membrane Protein Production and Structure Determination (P01, R01, R21) (RFA-RM-04-026).   See:https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-026.html

(5)  Membrane Protein Production and Structure Determination (R01) (RFA-7-003).  See:https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-07-003.html                  

(6)  Structural Biology Roadmap Website:  http://nihroadmap.nih.gov/structuralbiology/

(7)  Protein Structure Initiative.  See: http://www.nigms.nih.gov/psi/.

(8)  Specialized Centers for the Protein Structure Initiative (RFA-GM-05-002).  See: http://grants2.nih.gov/grants/guide/rfa-files/RFA-GM-05-002.html.

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the P50 Specialized Center Grant award mechanism.

The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed P50 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). 

2. Funds Available

The estimated amount of funds available for support of 2-3 P50 Center projects awarded as a result of this announcement is $5 Million for fiscal year 2009. Future year amounts will depend on annual appropriations.

The anticipated number of awards will be for 2-3 Centers.  Direct costs are limited to no more than $1.5 million for the first year.  The total project period for an application submitted in response to this funding opportunity may not exceed five years.  

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.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. 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

Applicants are not permitted to submit a resubmission application in response to this FOA.  Renewal applications will be permitted for this FOA. 

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

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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.

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. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

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

Applications Involving federal Agencies

The requests from federal agencies, including the NIH intramural program, will not include any salary and related fringe benefits for career, career conditional or other federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative costs).

In general, the budget requests will be limited to the incremental costs required for carrying out the proposed work.  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. While support for extramural collaborators may be requested in a separate grant application, funds can be requested for services by an external investigator or contractor as a subcontract/consortium including the applicable indirect (F&A costs) of the contractor/collaborating institution.

Justification must be provided for all requested support and for the Federal employees who will be committed to the project although no funds are requested in the application.

Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

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: September 21, 2008
Application Receipt Date: October 21, 2008
Peer Review Date: February/March 2009
Council Review Date: May 2009
Earliest Anticipated Start Date(s): August 1, 2009

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 PD/PI(s)
• 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 by e-mail or by fax to:

John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive
Building 45, Room 2AS-13B, MSC 6200
Bethesda, MD 20892
Telephone: (301) 594-0533
FAX: (301) 480-2004
E-mail: norvellj@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 five 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)

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

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 or renewal 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 or renewal 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.)

6. Other Submission Requirements and Information

Special Requirements

Center Structure:  The Center should support an integrated, coordinated program with various interdependent subprojects. The subprojects and cores must be fully described and justified.  Collaborations and consortia are encouraged.  In such collaborations, the respective contributions should be well integrated into the design of the application.

Subprojects for Methods Development: The goal of the Centers will be the technological development of innovative methods, reagents and approaches for the production of membrane proteins in a functional state for structure determination. This research should be set out as a series of specific, multidisciplinary subprojects, each focusing on different but complementary and novel approaches.  Additional goals of the Centers should be the availability and dissemination of the methods and reagents developed and the results generated to investigators within and outside the Centers.  These subprojects should be headed by an appropriately qualified investigator who may or may not be the overall Center program director (PD) and principle investigator (PI).  Not all subprojects need to begin in the first year.  Some may be phased in as progress on the initial subprojects allows.  A variety of approaches to each problem should be presented. 

Core Research Facilities:  The rationale for supporting a Center should be the common scientific objectives of the participants, not the support of a core facility.  However, a Center application may request support for scientifically justified facilities, including equipment and support personnel.  Plans should be presented for providing core access to all participants in the Center and for making unique Center facilities available to collaborating researchers outside of the Center participants.

Administrative Core:  A plan should be presented for the overall administration of the Center and for the prioritization, selection, deletion, and evaluation of subprojects, cores, methods, and approaches.  Plans for rapidly adjusting the Center priorities as projects succeed or fail should be outlined.  Methods and criteria for flexibly evaluating, initiating, and replacing cores and subprojects should be described.  The decision making process for disseminating reagents, methods and results should be presented.  The dissemination of results should take the form of a database, website or other appropriate information tool, as well as peer-reviewed publications.  The PI should indicate how the methods and open-source software developed by the Center will be available to the research community.  A plan should be presented for citation of Center support, determining authorship, and resolving other acknowledgement and intellectual property (IP) issues that may arise among participants and collaborators.  The PI has responsibility for the overall operation of the Center.  Delegated areas of responsibility should be clearly indicated.  Plans for any internal or external advisory committees should be specified.  Advisory committee members should not be identified or selected until after an award has been made, except in the case of on-going advisory structures. 

Information Sharing: It is expected that Center participants will publish and disseminate their results in the usual ways.  In addition, Centers should include plans to establish databases or websites for the purpose of sharing information, such as experimental protocols, materials, software programs, and results, including negative data that are not generally publishable in great detail. Plans for reducing positive data and outcomes to best practices should also be outlined. 

Outreach and Training:  A plan for outreach to the scientific community which may include scientific and technological workshops should be included.  In addition, plans for recruiting new investigators and under-represented minority students and trainees should be discussed. 

Annual Meeting: All Center participants should meet on at least an annual basis.  The meetings may be held at the home institution of the Center’s PI, or at one of the other participating institutions, or at another location, such as in conjunction with a relevant scientific meeting, or in Bethesda.  Travel funds to support this activity should be requested in the budget.  Funds should also be requested to help organize and attend an annual meeting for all investigators funded by the Roadmap Structural Biology initiatives.  NIH staff should be invited to participate in these meetings.  Other mechanisms should also be presented to assure regular communication and interaction between Center participants. 

Research Plan Page Limitations

The page limit for the research plan (including specific aims, background and significance, preliminary studies, and research design and methods) is increased to 60 pages total.

Appendix Materials

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

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: Regardless of the amount requested, investigators 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/.

Section V. Application Review Information

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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 CSR 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 a priority score.
• Receive a written critique.
• Receive a second level of review by the appropriate national advisory 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

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health.  In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?  

Investigators: Are the PD/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? 

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

In addition to the above review criteria, the following criteria will be applied to applications.

Interactions and Interdisciplinarity: Is there a sufficient degree of interaction among the subprojects and each subproject with the cores to create a Center which is more than the sum of its parts and has the potential to have high impact? To what degree is the goal of promoting multidisciplinary and interdisciplinary interactions among scientists achieved?

Plans for Evaluating and Prioritizing Subprojects and Scientific Cores: Are there adequate plans for selecting and evaluating a variety of subprojects and scientific cores for membrane protein production and structure determination, for tracking new ideas and development, and for modifying, adding or deleting subprojects and cores because of these new developments?

Plans for Making Center Facilities Available:  Are there adequate plans to make unique Center facilities, results, materials and methods available to collaborative researchers and to enhance collaborations?

Plans for the Overall Administration: Are there adequate plans for any internal or external advisory committees, for annual and strategic planning meetings, for all-hands Roadmap meetings, for assuring communication, interaction, and synergy among Center participants and the scientific community, and for handling intellectual property issues? Is the principal investigator committed to the center, its goals and subprojects?

Plans for Information Sharing:  Are there adequate plans for sharing of Center discoveries and data via databases, websites, distribution of software, training workshops, and other means of dissemination beyond the usual publication of results?

Plans for Outreach and Training:  Are there adequate plans for community outreach, and for the training and recruitment of new investigators and trainees, especially under-represented minorities, to research on the structure and function of membrane proteins?

NIH considers the following in evaluating Center grant applications:

• The scientific and technical merit of the proposed program;
• The qualifications and experience of the center director and other key personnel;
• The statutory and program purposes to be accomplished;
• The extent to which the various components of the proposed program would be coordinated into one multi-disciplinary effort within the center;
• The extent to which the center's activities would be coordinated with similar efforts by other organizations;
• The administrative and managerial capability of the applicant; and
• Other factors which the awarding IC considers appropriate in light of its particular statutory mission.

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Resource Sharing Plan(s)   

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

• Data Sharing Plan. [https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm] 
• Sharing Model Organisms. [https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

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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).

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.

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

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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:

John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Building 45, Room 2AS.13B
45 Center Drive
Bethesda, MD 20892
Telephone: (301) 594-0533
FAX: (301) 480-2004
Email: norvellj@nigms.nih.gov

2. Peer Review Contacts:

Donald L. Schneider, Ph.D.
Division of Molecular and Cellular Mechanisms
Center for Scientific Review
Rockledge I, Room 5160
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 435-1727
FAX: (301) 480-1988
Email: schneidd@csr.nih.gov 

3. Financial or Grants Management Contacts:

Ms. Grace Olascoaga
Grants Administration Branch
Division of Extramural Activities
National Institute of General Medical Sciences
Building 45, Room 2AN.32C
45 Center Drive
Bethesda, MD 20892
Telephone: (301) 594-5520
FAX: (301) 480-2554
Email: olascoag@nigms.nih.gov 

Section VIII. Other Information

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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 public 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. Applications that do not provide this information will be returned without review.

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 or Health Systems Agency review. 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.