Part I Overview Information

Department of Health and Human Services

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

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

Title: NIGMS Center for the Determination of Structures of HIV/Host Complexes (P50)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-GM-07-001

Catalog of Federal Domestic Assistance Number(s)
93.859

Key Dates
Release Date: April 13, 2006
Letters of Intent Receipt Date(s): December 13, 2006
Application Receipt Date(s): January 12, 2007
Peer Review Date(s): April 2007
Council Review Date(s): May 2007
Earliest Anticipated Start Date: July 1, 2007
Expiration Date: January 13, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

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 and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
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

The National Institute of General Medical Sciences invites applications for Centers that will support the determination of the structures of macromolecular components of the human immunodeficiency virus (HIV) complexed with macromolecular components of host cells.

From the time of entry into the host to final release, viral-host complexes play an integral role in the reproduction and proliferation of the virus. These complexes range from binary protein-protein and protein-nucleic acid complexes to much larger multicomponent complexes. A number of these interactions are documented in the HIV-1, Human Protein Interaction Database (http://www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions/). Although these structures offer the potential of providing intervention strategies for the treatment of AIDS, the first step towards the exploitation of these targets, the determination of their high resolution structures, has been accomplished in only a few cases. Thus the goal of this Request for Applications (RFA) is the creation of Centers dedicated to the determination of the high-resolution structures of these complexes. In order to succeed, these Centers must collaborate with the biological community doing research aimed at identifying and validating the presence of these complexes. The latter will be funded by existing mechanisms and a related Program Announcement (PA-06-388) published by the National Institute of Allergy and Infectious Diseases (NIAID).

The goal of this announcement is to attract the best scientists in relevant fields to attack the problem of the structure determination of HIV/host macromolecular complexes. Hence the application should focus on the specific problems to be solved, approaches to be used, identification of potential bottlenecks, a workable management plan along with milestones, and the commitment and past experience of the investigators. The research being proposed is expected to push the boundaries of what is feasible. As such, it is recognized that aspects of the plan necessarily will be highly risky.

Characteristics of each Center:

1. Each Center must have the demonstrated capabilities for the high resolution structure determination of macromolecular complexes.

2. Each Center must have a focus of investigation within the broader biology of HIV/host cell interactions. This focus will help to guide selection of structure determination targets.

3. Each Center must actively collaborate with the biological community engaged in research on HIV/host complexes.

4. Each Center is strongly encouraged to have a technology component designed to push the state-of-the-art in the cloning, expression and structure determination of HIV/host complexes.

5. Alternatively or in addition to 4 above, a Center may propose to study the role and/or activity of certain complexes in vivo using state-of-the-art biophysical techniques.

Details on each of the above characteristics are given below:

1. Structure determination: X-ray crystallography is generally the method of choice for determining the structures of macromolecular complexes. However, it often may be useful to employ other methods either alone or in conjunction with x-ray crystallography. For example, nuclear magnetic resonance may be the method of choice for structure determination in certain instances or may be used to determine interfaces between subunits whose individual structures have been determined by x-ray crystallography. Likewise, electron microscopy may be used to determine moderate resolution structures of complexes or may be used to provide envelopes into which higher resolution models of subunits can be docked. Small angle x-ray scattering and other methods also may play important roles. Given the scope of the research to be undertaken, each Center must have available a range of structure determination methods, from routine to more advanced. It is expected that methods unique to a Center will be made available to the other Center(s) on a collaborative basis.

The determination of the structures of macromolecular complexes requires control over all aspects of sample preparation, including cloning, expression or synthesis, purification, and for crystallography, crystallization. Success in these steps often is determined by trial and error methods in which many experimental conditions are systematically varied. As has been shown by various structural genomics efforts throughout the world, there is tremendous advantage to automating many of the procedures. For some aspects of sample preparation, it may make sense to carry out the procedures in house. For other aspects, it may make more sense to tap into an existing structural genomics pipeline through a collaborative agreement. Applicants are strongly encouraged to establish such collaborations.

2. Biological focus: The proposed research should aspire to achieve a comprehensive structural analysis of a particular aspect in the biology of HIV-host cell interactions. A judiciously selected set of structures will provide a sufficiently extensive and detailed framework for interpreting, integrating, and guiding functional research related to that aspect of HIV biology. Through such a focused approach, a deep and definitive understanding of that aspect of HIV biology should emerge that then may be capitalized effectively for therapeutic strategies. Since in certain cases related systems, such as other lentiviruses, may be more tractable for structure determination, work on such is acceptable. In these cases, the work must contribute demonstrably to our understanding of HIV biology and provide lessons that can be applied to the development of anti-HIV therapeutics.

3. Collaboration: The set of possible targets for structure determination is very large. Thus, it is unreasonable to expect the Centers, even when considered together, to possess the biological expertise to explore and develop all such targets. It, therefore, is essential that each Center have a mechanism and infrastructure for establishing and maintaining collaborations with outside scientists studying HIV/host interactions. These collaborators should be able to enter the structure determination pipeline at several points, from the provision of clones to actual purified complexes. The collaborators expertise in the biological aspects may also be important as the Centers attempt to bring the particular biological system under the control needed for structure determination. Conversely, investigators pursuing functional studies of HIV host cell interactions are being encouraged to collaborate in structural studies with the Centers through a Program Announcement published by NIAID (PA-06-388). Through these multiple avenues for collaboration, the goal is to mesh structural and functional studies of HIV host interactions such that they inform and build on each other in pursuit of effective anti-HIV therapeutics. Thus, it is expected that potential competitors will collaborate to the benefit of the project as a whole.

4. Technological Component: The determination of the structure of macromolecular complexes pushes the current state of the art, both in terms of the technology needed for structure determination and the biology needed to produce sufficient material for analysis. Hence each Center is encouraged strongly to have a component devoted to advancing the state of the art of the determination of structures of macromolecular complexes. While well-behaved non-HIV related macromolecular complexes may be appropriate to develop and validate new methods, the methods developed must be clearly applicable to the determination of the structures of HIV/host complexes.

5. In vivo role: Modern single-particle methods are being used increasingly to examine biological processes in vivo. A Center may include a component to study role of HIV/host complexes in the lifecycle of the virus in real time using such imaging methods. For this component, collaboration with scientists with demonstrated expertise in these methods is recommended strongly.

Management and Oversight

Because of the complex nature of these Centers, the Principal Investigator must devote at least 25% of his/her effort to the project. It is also essential that significant effort and enthusiasm be exhibited by other key personnel. Because of the complex nature of these Centers, support of a Center coordinator, who will attend to the day-to-day operation of the Center, is strongly encouraged. If Collaboration Development Funds (see Section IV.6-Other Submission Requirements) are requested as part of the budget, then an explanation of the process by which fund use will be decided must be provided.

Overall success of this program depends critically on the success of each Center, the accomplishments of collaborating investigators and on the ability of the entire program to work in concert.

Therefore:

Each Center will appoint an advisory committee in consultation with and subject to the approval of the NIGMS Program Official. This advisory committee will meet at least once a year and give advice directly to the Center. The NIGMS Program Official will attend each meeting of the advisory committee as an observer. Candidates for the advisory board should not be named in the application or solicited prior to award.

In addition, NIGMS and the Division of AIDS, NIAID will appoint an advisory committee to oversee the operation of the entire network. That committee will be a subcommittee of the National Advisory General Medical Sciences Council. Members of this committee will be appointed directly by the Program Officials of NIAID and NIGMS and will give advice directly to NIH. The committee will meet at least annually. Representatives from each Center are required to attend.

To ensure coordination and cooperation among the funded Centers and the other members of the scientific research community working in areas germane to the mission of the Centers, an annual scientific meeting will be held. Attendance of the principal investigator and key participants from each Center is required. Attendance of key collaborating investigators is highly encouraged. Sufficient funds should be included in the budget for travel to these meetings.

The collaborative aspects of the overall program are essential for its success. Given the dynamic nature of collaborations, this aspect is expected to change from year to year. Therefore, each Center must update its plans for collaboration each year. These updated plans for collaborations will be reviewed by the Advisory Committee and approved by the NIGMS Program official. This approval will be a condition of the award. In the event additional funds become available, support could be provided for innovative approaches that are conceived after the onset of the Center grant.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the P50 Center award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

2. Funds Available

NIGMS intends to commit up to 10,000,000 dollars total costs in FY 07 to fund two or three applications in response to this RFA. An applicant may request a project period of up to five years and a budget for direct costs of up to 2.7 million dollars per year and for total costs up to four million dollars per year. Although the financial plans of the NIGMS provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

Only one application may be submitted from an applicant organization.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their 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.

2. Cost Sharing or Matching

Cost sharing is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Not applicable

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 on line 2 of the face page of the application form and the YES box must be checked.

The instructions for the Research Plan section of the application should be modified as follows: The overall page limit for the Research Plan section (excluding the Bibliography) of the application is 60 pages. This overall limit must be adhered to strictly. The page limits given below for each subsection are recommendations. Given the page limits, experimental details should be provided to the extent it is felt necessary to provide confidence that the research plan is reasonable and that likely hurdles and potential solutions have been considered carefully.

Section 1--Center in its entirety using the following sections:

Specific Aims: In one page, the specific aims should be presented for the Center as a whole.

Background and Significance: In up to five pages, the proposal should present relevant background information, biological problems and technological problems that need to be solved to push the field forward.

Preliminary Results and Progress Report: In up to three pages, describe the expertise of the key participants and provide references to their significant relevant publications.

Approach: In up to seven pages, present the rationale for the organization of the Center, the rationale for the inclusion of each investigator, a management plan and milestones for each year of research proposed. Justify the length of award sought. If Collaboration Development Funds (see Section IV.6-Other Submission Requirements) are requested in the budget, then a plan for potential uses and the process by which fund use decisions will be made must be included.

Section 2--Biological Theme:

Specific Aims: In one page, outline what you wish to accomplish over the term of the grant.

Background and Significance: In up to three pages, the application should place the proposed studies in the context of the field and the Center.

Preliminary Results: In up to five pages, outline the experience of the group in the area of the biological theme. Cite relevant key publications. Any unpublished preliminary results should be presented briefly.

Approach: In up to seven pages, outline the approach to be taken to further knowledge on the biological theme. Included should be milestones and a delineation of the likely major bottlenecks to be encountered. Possible approaches to be taken should be given and at a level of detail sufficient to provide reasonable confidence that the bottlenecks can be overcome.

Section 3--Collaborations:

In up to four pages describe the mechanisms and infrastructure that will be used to establish and maintain collaborations with the scientific community engaged in the identification, validation and study of HIV/host complexes. This section should document existing collaborations. Letters of collaboration and collaborators biosketches should be included in the appendix material. It is essential that sufficient travel funds be allocated in the budget for the collaborations envisaged.

Next Section(s)--Technological component(s) and/or single particle in vivo imaging:

Specific Aims: Use one page. For a technological component, outline the technological barriers to be overcome. For in vivo imaging, outline the goals of the in vivo imaging approach.

Background and Significance: Use up to three pages. For a technological component, describe the problem or barrier the technological advances will solve or overcome and the advantage of the technological advances will have over existing technology. For in vivo imaging, place the proposed studies in the context of the field and the Center.

Preliminary results: Use up to five pages. Outline the experience of the group in the area of the biological theme. Cite relevant key publications. Any unpublished preliminary results should be presented briefly.

Approach: Use up to seven pages. Outline the approach to be taken. Included should be milestones, a delineation of the bottlenecks to be encountered, the kinds of expertise required and the steps taken to acquire that expertise, either by direct participation or collaboration. Possible approaches to circumvent potential bottlenecks should be described.

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: December 13, 2006
Application Receipt Date(s): January 12, 2007
Peer Review Date: April 2007
Council Review Date: May 2007
Earliest Anticipated Start Date: July 1, 2007

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 at the beginning of this document.

The letter of intent should be sent to:

Ravi Basavappa, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive
Building 45, Room 2As.19E
Bethesda, MD 20892
Telephone: (301) 594-0828
FAX: 301-480-2004
Email: basavapr@nigms.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications 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)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

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

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIGMS. Incomplete and 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 http://grants.nih.gov/grants/policy/policy.htm.

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 competing continuation award if such costs: are necessary to conduct the project, and 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 competing continuation 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

Annual Meeting. Applications should include travel funds for the appropriate personnel to attend an annual meeting and the annual advisors meeting

Letters of collaboration and collaborator biosketches must be provided as appropriate. The letters of collaboration must document the extent of the collaboration.

Collaboration Development Fund: To provide flexibility in establishing new or strengthening existing collaborations, applicants may request part of their budget be allocated to a Collaboration Development Fund. Such a fund will allow within a fiscal year rapid funding changes that may be necessary to keep pace with the dynamics of new and existing collaborations. The fund should be used primarily to support staff and purchase equipment or supplies. All expenditures from the Collaboration Development Fund must be approved by NIH staff. Applicants may request up to 5% of the total annual budget be allocated to this fund.

Plan for Sharing Research Data

All data must be made available to the public in a timely manner. All coordinates and structure factors or NMR resonance assignments and restraints resulting from research supported by funds from this RFA, whether the project originated in the Center or in the laboratory of a collaborator, must be available from the Protein Data Bank or BioMagResBank on publication. Structures of protein complexes solved by electron microscopy using funds from this RFA must be submitted to the EMDB database.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

The following will be considered in making funding decisions:

Program priorities and balance will be an especially important selection criterion. That is it may be the case that a more highly ranked application may passed over in favor of a less highly ranked one to achieve a balance in targets, methods and approach.

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Center for Scientific Review (CSR) in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

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 high 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? Are the scientific methods and approaches proposed appropriate? Are the plans for project coordination and collaboration adequate?

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? Does the project strike an appropriate balance between using established methods and developing innovative approaches? Will the innovative approaches proposed benefit the field of HIV-related research?

Investigators: Are the investigators 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 investigative team bring complementary and integrated expertise to the project (if applicable)? What is the record of the investigators in developing innovative approaches to similar projects? What is the level of enthusiasm and commitment of the participants for the project?

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? Is the environment conducive to the establishment of collaborations with the larger participating scientific community? Is the organization of the Center sufficient to meet the goals of this RFA?

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 priority score:

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 E on Human Subjects in the PHS Form 398).

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 E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions 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. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates

N/A

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

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 PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Ravi Basavappa, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive
Building 45, Room 2As.19E
Bethesda, MD 20892
Telephone: (301) 594-0828
FAX: 301-480-2004
Email: basavapr@nigms.nih.gov

2. Peer Review Contacts:

Ranga V. Srinivas, Ph.D.
Chief, AIDS & Related Research IRG
Center for Scientific Review, N.I.H.
6701 Rockledge Drive
Room 5222, MSC 7852
Bethesda, MD 20892-7852 (Use 20817 for FedEx)
Phone: 301-435-1167
FAX: 301-480-2241

3. Financial or Grants Management Contacts:

Grace Olascoaga
Chief Grants Management Officer
National Institute of General Medical Sciences
Building 45, Room 2An.32C
45 Center Drive
Bethesda, MD 20892
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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.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at 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:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).

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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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 PA 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.

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NIH Funding Opportunities and Notices


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