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 Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov/)
National Institute of Neurological Diseases and Stroke (NINDS) (http://www.ninds.nih.gov/)
National Institute of Allergy and Infectious Diseases (NIAID) (http://www.niaid.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www.niddk.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (http://www.niams.nih.gov/)
National Institute of General Medical Sciences (NIGMS) (http://www.nigms.nih.gov/)
National Institute of Dental and Cranofacial Research (NIDCR) (http://www.nidcr.nih.gov/)

Title: Biology of RNA Interference: Stability, Delivery and Processing by Tissues

Announcement Type
New

Request For Applications (RFA) Number: RFA-HL-05-019

Catalog of Federal Domestic Assistance Number(s)
93.837, 93.838, 93.839, 93.853, 93.846, 93.859, 93.121, 93.855

Key Dates
Release Date: August 2, 2005
Letters of Intent Receipt Date(s): December 21, 2005
Application Receipt Dates(s): January 18, 2006
Peer Review Date(s): June–July, 2006
Council Review Date(s): September 7, 2006
Earliest Anticipated Start Date: September 30, 2006
Expiration Date: January 19, 2006

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, 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

 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 purpose of this RFA is to stimulate research towards (1) understanding uptake and processing of RNAi by target tissues, (2) assessing stability, half-life and off-target effects in target tissues, and (3) determining optimal delivery methods for uptake by the target tissues.

RNA interference (RNAi) is an effective post-transcriptional strategy for silencing genes. It is a naturally occurring post-transcriptional strategy used by cells to silence genes. Silencing is induced through short sequences of double-stranded RNA that are typically 21-23 nucleotides in length. Studies on plants, worms, fruit flies, mice, and human cells suggest that the RNAi process is conserved among invertebrate and vertebrate species. RNAi has become a powerful molecular tool since the demonstration that exogenous application of small interfering RNAs (siRNAs) to mammalian cells leads to effective silencing of the targeted gene. This approach has been used to generate cells, tissues, and animals with reduced expression of specific genes and has helped determine the function of candidate genes. Animal studies indicate that RNAi holds great therapeutic potential for a wide range of diseases. The potential therapeutic applications of RNAi are broad and range from viral infections to genetic disorders. Promising results in gene silencing have already been shown in viral diseases (such as HIV/AIDS, influenza, and human papillomavirus infection), cancer, inflammatory diseases (such as rheumatoid arthritis), neurodegenerative diseases, and autoimmune diseases (such as type 1 diabetes mellitus).

RNAi tools could prove valuable in moderating the pathophysiology of many disease states. Preliminary studies also suggest beneficial effects in improving stroke therapy as well as in helping dilated cardiomyopathy patients through enhanced survival of myocardial endothelial cells. RNAi approaches also offer to overcome the thrombotic effects of antibodies in countering acute or chronic inflammatory states. RNAi targeting of the ApoB mRNA has been shown to lower total cholesterol levels in mouse models. Similar RNAi targeting approaches are being tested in asthma and for therapeutic interventions in pulmonary hypertension. RNAi also provides a potential approach to treat dominantly inherited diseases where the mutations are heterogeneous, such as neurofibromatosis or tuberous sclerosis, and for polygenic diseases, such as Parkinson's disease or Alzheimer's disease. In these cases, knowledge of molecular pathways may provide alternative targets for RNAi where, for example the activity of a suppressor gene has been disrupted.

While RNAi inhibits the expression of genes in a sequence-specific manner, issues of specificity and processing are not yet clear. The potential of RNAi as a therapeutic tool is due to the ubiquitous presence of the enzymatic machinery necessary to process microRNA. Since this machinery is predominantly used in mammalian cells for microRNA mediated gene regulation, the use of siRNA might produce differential effects during interaction with the silencing complexes. These effects may differ across tissues as well. Uptake, stability, and processing may differ among various tissues and this RFA focuses on addressing these issues specifically relevant to the mission of the participating Institutes. The off-target effects and toxicities of RNAi in these tissues need to be understood to fully realize the therapeutic potential of RNA interference. Off-target effects of RNAi include the activation of innate immune pathways, suppression of non-targeted genes, and regulation of protein expression without corresponding effects on mRNA. One important barrier to RNAi-based therapeutics is the effective delivery of RNAi to target tissues. While a number of strategies have been developed to deliver siRNAs, effective approaches to in vivo delivery to most target organs are lacking. This RFA is also intended to support the development of novel and highly efficient delivery methodologies.

Appropriate topics for investigation under this RFA include but are not limited to:

The participating Institutes have interests in biology relevant to the physiologic systems within their missions and are specified below:

NHLBI: Research focusing on the cell, tissue types and organs relevant to the NHLBI mission includes the cardiovascular system, pulmonary system, sleep-regulating systems, and blood systems.

NINDS: Applications should focus on targeting tissues and cell types of the nervous system affected in neurological disorders. A partial list of diseases (including neurodegenerative disorders, brain tumors, HIV-dementia) that is relevant to the research missions of NINDS is given in Appendix A of the planning document “Neuroscience at the New Millennium” (http://www.ninds.nih.gov/about_ninds/strategic_plan.htm). In addition, The NINDS is also interested in overcoming the difficulty of delivering therapeutic agents across the blood brain barrier to specific regions of the brain. The use of RNAi to manipulate the permeability of endothelial cells in the brain microvasculature and their interactions with brain cells of the neurovascular unit is of interest to NINDS.

NIAID: Research of interest should focus on the use of RNA interference to regulate host-pathogen interactions. These studies should be focused on one of the following areas: (1) the innate immune system including, but not limited to, the regulation of innate immune cells (e.g., macrophages, dendritic cells, NK and NK T cells) or expression and signaling through innate immune receptors, such as Toll-like Receptors, NK regulatory receptors, and other regulatory receptors; or (2) NIAID Category A-C pathogens (http://www2.niaid.nih.gov/Biodefense/bandc_priority.htm) including, but not limited to, the study of inhibition of pathogen genes and protein expression in vivo ; and prevention of virus assembly, budding, or release.

NIDDK: Research focusing on cell types relevant to the NIDDK mission includes those of the endocrine, liver, kidney, gastrointestinal, urologic, and hematological systems. This may include, but is not limited to, studies related to insulin resistance, obesity, inborn errors of metabolism, autoimmune disease such as type 1 diabetes or Crohn's Disease, diabetic neuropathy, acute renal failure, benign prostate hyperplasia, hepatitis, or cystic fibrosis.

NIAMS: Research of interest to the NIAMS includes work with potential relevance to the treatment of diseases and injuries affecting muscle, bone, joints, connective tissue, and skin. Of particular interest for gene silencing approaches are pathologies arising from autosomal dominant genetic defects, or from aberrant immune or inflammatory processes.

NIGMS: Research that addresses the basic mechanisms of RNAi stability, delivery, and uptake by cells is of interest to the NIGMS.

NIDCR: Research of interest to NIDCR includes projects focusing on oral, dental and craniofacial tissues, including the temporal mandibular joint, with relevance to the treatment and repair of injuries to these tissues, as occurs in oral diseases and congenital disorders.

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 NIH investigator-initiated Research Project Grant (R01) and the Exploratory/Development Research Grant (R21) award mechanisms . The total requested project period for an application submitted in response to this RFA may not exceed four years for the R01 mechanism and two years for the R21 mechanism. This RFA is a one-time solicitation. The R21 mechanism is intended to encourage new exploratory/developmental research projects by providing support for the early stages of their development. Awards are made to demonstrate feasibility of a subsequent project and to obtain preliminary data testing innovative ideas. Therefore, these grants are not renewable. Continuation of projects developed under this program will be through the regular research project grant mechanism (for example, R01). These grants are not intended to support or supplement ongoing funded research of an established investigator, or to serve as an alternative mechanism of support for projects not receiving funding as competitive continuation applications. The R01 award represents an investigator-initiated research grant designed to support a discrete, specified research project performed by a principal investigator.

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

This funding opportunity uses just-in-time concepts. It also uses the modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/modular/modular.htm).

2. Funds Available

The National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Neurological Diseases and Stroke (NINDS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of General Medical Sciences (NIGMS), and the National Institute of Dental and Cranofacial Research (NIDCR) intend to commit approximately $5.6 million dollars in FY 2006 to fund 13-17 new grants in response to this RFA. The NHLBI intends to commit approximately $1.5 million in FY 2006 for this announcement to support 4-5 meritorious applications. The NINDS intends to commit approximately $1.5 million in FY 2006 for this announcement to support 4-5 meritorious applications. The NIAID intends to commit approximately $1.0 million in FY 2006 for this announcement to support 2-3 meritorious applications. The NIDDK intends to commit approximately $0.4 million in FY 2006 for this announcement to support one meritorious application. The NIAMS intends to commit approximately $0.4 million in FY 2006 for this announcement to support one meritorious application. The NIGMS intends to commit approximately $0.4 million in FY 2006 for this announcement to support one meritorious application. The NIDCR intends to commit approximately $0.4 million in FY 2006 for this announcement to support one meritorious application.

An applicant may request a project period of up to two years for the R21 mechanism and up to four years for the R01 mechanism. In the case of R21 awards, the combined budget for direct costs for the two-year project period may not exceed $275,000. For example, you may request $100,000 in the first year and $175,000 in the second year to meet the needs of your project. Normally, no more than $200,000 may be requested in any single year. In the case of R01 applications, direct costs may not exceed $250,000 per year. The anticipated start date of new awards is September 30, 2006.  

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 NHLBI, NINDS, NIDDK, NIAMS, NIGMS, NIDCR, and NIAID 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.

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:

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 programs.

2. Cost Sharing or Matching
Not applicable

3. Other-Special Eligibility Criteria

Annual Grantee Meeting

Upon initiation of the program, the NIH will arrange annual meetings to encourage the exchange of information among the investigators who participate in this program. In the preparation of the budget for the grant application, applicants should include travel funds for one meeting each year to be held in Bethesda, MD. Applicants should also include a statement in the application indicating their willingness to participate in such meetings.

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) 435-0714, 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.

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

Letters of Intent Receipt Date(s): December 21, 2005
Application Receipt Dates(s): January 18, 2006
Peer Review Date(s): June–July, 2006
Council Review Date(s): September 7, 2006
Earliest Anticipated Start Date: September 30, 2006

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:

Pothur Srinivas, Ph.D., MPH
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Diseases
6701 Rockledge Drive, Room 10188
Bethesda, MD 20892
Telephone: (301) 435-0550
FAX: (301) 480-2858
Email: ps241q@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 NHLBI. 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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

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/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Specific Instructions for Modular Grant applications.

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing; the format of the final dataset; the documentation to be provided; whether or not any analytic tools also will be provided; whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use); and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

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.

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/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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

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

The following will be considered in making funding decisions:

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 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?

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 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)?

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?

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:

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/archive/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
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

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/archive/grants/policy/nihgps_2003/index.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 14 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 Notice of Award. 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/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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:

Pothur Srinivas, Ph.D., MPH
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Diseases
6701 Rockledge Drive, Room 10188
Bethesda, MD 20892
Telephone: (301) 435-0550
FAX: (301) 480-2858
Email: ps241q@nih.gov

Danilo A. Tagle, Ph.D.
Neurogenetics Program
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2133
6001 Executive Boulevard
Bethesda, MD 20892
Telephone: (301) 496-5745
FAX: (301) 402-1501
Email: tagled@mail.nih.gov

Lynda Chiodetti, Ph.D.
Immunoregulation Section
Division of Allergy, Immunology, and Transplantation
Basic Immunology Branch,
National Institute of Allergy and Infectious Diseases
6610 Rockledge Drive, Rm 3006
Bethesda, MD 20892-6601
Telephone: (301) 451-3119
FAX: (301) 480-2381
Email: lchiodetti@niaid.nih.gov

Rebekah S. Rasooly, Ph.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 643
Bethesda, MD 20892
Telephone: (301) 594-6007
FAX: (301) 480-3510
Email: rasoolyr@mail.nih.gov

William J. Sharrock, Ph.D.
Bone Biology Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5055
FAX: (301) 480-4543
Email: sharrocw@mail.nih.gov

Marcus Rhoades, Ph.D.
Division of Genetics and Developmental Biology
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-0943
FAX: (301) 480-2753
Email: greenbj@mail.nih.gov

Rochelle K. Small, Ph.D.
Developmental Biology and Genetics Program
National Institute of Dental and Cranofacial Research
Natcher Building, Room 4AN-18D
Bethesda, MD 20892
Telephone: (301) 594-9898
FAX: (301) 480-8318
Email: Rochelle.small@nih.gov

2. Peer Review Contacts:

Sally Amero Ph.D.
Chief, Bioengineering Sciences and Technologies IRG
Center for Scientific Review
6701 Rockledge Drive, Room 4190
Bethesda, MD 20892-7849 (Express zip: 20817)
Telephone: (301) 435. 1159
FAX: (301) 480.4042
Email: ameros@csr.nih.gov

3. Financial or Grants Management Contacts:

Norma Deguzman
Grants Operations Branch
National Heart, Lung, and Blood Institute
Rockledge II, Room 7167
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 496-6740
FAX: (301) 480-3310
Email: deguzman @nhlbi.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.

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/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004, receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.