EXPIRED
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.
Table of Contents
Part I
Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity
Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility
Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and
Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated
Start Dates
1.
Letter of Intent
B. Sending an Application to
the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements 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
Section I. Funding Opportunity Description
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:
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: http://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: http://grants.nih.gov/grants/guide/pa-files/PA-07-280.html and http://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: http://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:http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-026.html
(5) Membrane Protein Production and Structure Determination (R01) (RFA-7-003). See:http://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
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 http://grants.nih.gov/grants/funding/phs398/phs398.html).
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 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
1.A. Eligible Institutions
The following
organizations/institutions are eligible to apply:
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see 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 http://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
1. Address to
Request Application Information
The PHS 398 application
instructions are available at http://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:
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 http://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 http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.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 http://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 http://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 http://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 http://grants.nih.gov/grants/gwas/.
Section V. Application Review Information
1. Criteria
Only the review
criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and responsive to the FOA will
be evaluated for scientific and technical merit by an appropriate
peer review group convened by 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:
The following will be considered in making funding decisions:
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:
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.
3. Anticipated Announcement and Award
Dates
Not
Applicable
Section
VI. Award Administration Information
1. Award Notices
After the peer review
of the application is completed, the PD/PI will be able to access his or her
Summary Statement (written critique) via the eRA Commons.
If the application is under consideration for funding,
NIH will request "just-in-time" information from the applicant. For
details, applicants may refer to the NIH
Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards,
Subpart A: General.
A
formal notification in the form of a Notice of Award (NoA) will be
provided to the applicant organization. The NoA signed by the grants management
officer is the authorizing document. Once all administrative and programmatic
issues have been resolved, the NoA will be generated via email notification
from the awarding component to the grantee business official (designated in
item 12 on the Application Face Page). If a grantee is not email enabled, a
hard copy of the NoA will be mailed to the business official.
Selection of an
application for award is not an authorization to begin performance. Any costs
incurred before receipt of the NoA are at the recipient's risk. These costs may
be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.
2. Administrative and National
Policy Requirements
All NIH grant and
cooperative agreement awards include the NIH Grants Policy Statement as part of
the NoA. For these terms of award, see the NIH Grants Policy Statement Part II:
Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.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.
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
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 (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
as mandated by the Health Research Extension Act of 1985 (http://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, http://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 (http://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 http://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 http://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 http://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 http://grants.nih.gov/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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://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 (http://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 http://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 http://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 (http://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 http://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 http://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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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