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 Dental and Craniofacial Research (NIDCR), ( http://www.nidcr.nih.gov)

Title: Building the Tooth: Bridging Biology and Material Sciences. (Limited Competition)[U54]

Announcement Type
New  

Request For Applications (RFA) Number: RFA-DE-07-009

Catalog of Federal Domestic Assistance Number(s)
93.121

Key Dates
Release Date: October 26, 2006
Letters of Intent Receipt Date(s): December 29, 2006
Application Receipt Date(s): January 29, 2007     
Peer Review Date(s): April, 2007
Council Review Date(s): May, 2007  
Earliest Anticipated Start Date(s): July, 2007
Expiration Date: January 30, 2007


Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

The National Institute of Dental and Craniofacial Research (NIDCR) invites Specialized Center-Cooperative Agreement (U54) applications to establish a National Center focused on Building a Tooth by Bridging Biology and Material Sciences (BTBBMS).  The specific objective of this initiative is the complete characterization of teeth and their supporting tissues as an integrated biological and biomechanical system that can provide the engineering specifications and design principles required to create blueprints for the design of new teeth and their associated structures. 

The broad scope of this initiative requires the efforts of well-integrated, interdisciplinary teams of investigators. Therefore, the U54 BTBBMS will involve scientists with significant expertise in cell and developmental biology, genomics and proteomics, chemistry, material sciences, biophysics, and engineering as well as computational sciences.  The BTBBMS will include three components:  1) the Organization and Management Component; 2) the Research Component; and 3) the Specialized Resources Component.  Each component will be reviewed separately and receive a priority score. The NIDCR may select the most meritorious component from each application to form an outstanding National Center on Building a Tooth by Bridging Biology and Material Sciences (BTBBMS).

This is a limited competition and as such only the three currently supported P20 grantees are eligible to apply (the process was described in RFA DE-06-002 http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-06-002.html ) The grant number and affiliation of each P20 grantee are: 1 P20 DE017447-01 Univ. of Illinois at Chicago; 1 P20 DE017453-01 Brigham & Women's Hospital and 1 P20 DE017460-01 Univ. of Southern California.

Telecommunications for the hearing impaired is available at: TTY 301-451-5936.  

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
    A. Cooperative Agreement Terms and Conditions of Award
      1. Principal Investigator Rights and Responsibilities
      2. NIH Responsibilities
      3. Collaborative Responsibilities
      4. Arbitration Process
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

This program underscores the desire of NIDCR to integrate biological and engineering sciences to provide the engineering specifications required to create blueprints for engineering a functional tooth. Substantial advances in genetics, developmental biology, bioengineering and material sciences have made it realistically possible to plan the regeneration of a functional tooth as a biomechanical system.

This limited competition provides the opportunity for the P20 PIs and their team members to continue their efforts in creating new approaches to complete the characterization of teeth and their supporting tissues as an integrated biological and biomechanical system.  It is anticipated that any one application would provide a complete view of the present and future understanding of tooth development in the context of the goal of designing engineering strategies for enabling tooth regeneration. Moreover, the successful applicants must clearly enunciate the design criteria for a successful engineered tooth.

The U54 funding mechanism and the intended BTBBMS structure promote integration of resources and expertise to facilitate synergistic and creative scientific interactions, while allowing research objectives that would maximize individual unique scientific strengths of each research team.

Background

By the age of 50 years, the average American has lost approximately 8 teeth (DHHS Report, 2000). By age 65, approximately 35% of the population is edentulous.  Treatment for tooth loss often involves dentures, whose long-term use results in bone resorption of the underlying jaw. Alternative treatments offered by oral surgeons include replacement of lost teeth with dental implants or rarely autologous tooth re-implantation.  Approximately 74 million US adults are potential candidates for dental implants.  Dental implant procedures are expensive (ranging from $2,000 for a single tooth to $25,000 for an entire jaw), are at times uncomfortable, and frequently eventually fail.  For example, the American Academy of Oral and Maxillofacial Surgery defines implant success as 85-90% survival of the implant for only 5-10 years.    

Implant failure can have a large economic impact on the patient, particularly since subsequent re-implantation becomes increasingly difficult.  Integrated, multidisciplinary approaches to tooth regeneration will be needed to develop new therapeutic strategies (based on biological principles) to meet the pressing patient needs concerning tooth replacement. 

The generation of a tooth relies upon a sequence of closely regulated and reciprocal signaling interactions between the ectoderm lining the future oral cavity and neural crest-derived ectomesenchymal cells, followed by precisely choreographed cell interactions with extracellular matrix molecules to generate the tooth and its crucial supporting structures.  New genes and their encoded structural and regulatory proteins governing these events have been discovered, and their function(s) have been characterized.  Nanostructures and nanomachines on the cell surface have recently been discovered that control the deposition of matrix and the movement of cells.  Although considerable progress has been made over the last decade in identifying the individual molecular mechanisms involved in early dental development, areas remain where relatively little is known about their integrated activities resulting in a functional tooth.

An added challenge is the understanding of the mechanisms that regulate the fabrication of highly ordered biocomposite ceramic material such as enamel, dentin, cementum and bone. For example, enamel formation has been well-studied in part because it is an ideal system for identifying the factors that specifically control biomineralization and because much is known about enamel proteins, their gene regulation, self-assembly into a matrix, and role in directing mineral crystal deposition.  However, enamel is possibly the most difficult target in tooth regeneration because it has no intrinsic cellular capacity to undergo self-repair. To date, substantial progress has been made in using basic principles of biomineralization to accomplish controlled processing of engineering materials that may be used to repair enamel lesions. 

In the 21st century, the field of biomaterials is one of the most exciting areas of bioengineering.  To date scientists can design and fabricate new materials following upon, and even improving the work of nature to meet the challenges of repairing, and restoring tissues and organs.

Modern technologies provide totally new avenues to systematically analyze the physical aspects of biological systems and cellular functions, (at the atomic, nanoscale and microscopic levels) and innovative approaches are emerging that allow the dissection of the mechanical infrastructure, thermodynamic behavior and control of physical and biological networks of tooth development and anchorage. A deeper understanding of the engineering principles of biological systems on the nanometer scale and how physical factors co-regulate cellular activities is likely to result in major progress toward understanding how cells function within the complex system. Moreover, the manipulation of the biological processes of tooth development and dynamic adult anchorage, at each size scale and complexity level, are becoming feasible. We anticipate that the collection of precise quantitative data will help develop the concepts, models, and physical tools required for tooth regeneration.  In addition, novel computational methods involving modeling and simulation by both computer and experimental tissue models using inputs from physical measurements will reveal additional links and interactions between molecules, assemblies and networks that had not previously been recognized.

Special Features and Research Objectives of the U54 BTBBMS Program

1. Organization and Management. Multidisciplinary Expertise of BTBBMS Teams. The BTBBMS will provide an organizational structure specifically designed to facilitate multidisciplinary interactions among investigators focused on the ultimate goal of discovering the engineering specifications and design principles required to create blueprints for the design of new teeth and their associated structures. 

The structure of the BTBBMS U54 is designed to provide investigators with the means of conducting multidisciplinary research in a highly collaborative atmosphere with consistent access to expertise, and minimal wasted time and effort. Key personnel of the BTBBMS U54 may comprise scientists from a variety of fields including, but not limited to: cell and developmental biology, genomics and proteomics, chemistry, material sciences, biophysics, and engineering as well as computational sciences. Most importantly, BTBBMS personnel must demonstrate an eagerness to collaborate outside of their own disciplines. The nature of these interactions will be determined by the applicants, and emphasis will be placed on establishing creative, productive, and synergistic interactions with eventual clinical impact.

2. Research Components. The Research Components must focus on all of the following subproject areas: a) cell and developmental biology; b) material and engineering sciences; and c) computational sciences. 

The growth of the tooth involves complex issues of developmental biology and materials science. A complete understanding of tooth development includes knowledge of what gene products are structurally or catalytically critical at different stages of tooth development, and what issues in material science and engineering are involved in understanding the structure of the tooth in different stages of development. Both top-down and bottom-up approaches should be considered for collecting the design specification needed to build a functional tooth. Applicants may consider different approaches for building a tooth. Whatever the approach might fall under, specific areas need to be addressed. For example, under a) cell and developmental biology, applicants should consider topics such as, but not be limited to: i) the genetic and developmental mechanism involved in the different stages of tooth formation; ii) a description of how gradients of composite ceramic materials such as enamel, dentine, cementum and bone are formed at different scales and how they integrate to form a functional tooth; iii) the development of tests and models to verify whether regenerated tooth or tooth structures possess the mechanical properties of natural teeth and; iv) a description of the methodologies to be used for the identification and selection of progenitor cells, genetically engineered cells and stem cell lines and; v) a description of how stem cell research will enhance the genomics/proteomics and new materials development aspects of the project.

The development of a blueprint with all the design specifications to engineer a tooth requires information from biology. Thus under b) material and engineering sciences applicants should consider topics such as, but not be limited to: i) description of contemporary and innovative technologies to capture and manipulate biological processes as they occur in vivo, as well as in vitro assays for further analysis and manipulation of such cellular processes; ii) the engineering of materials with surface and architecture characteristics that support the regeneration of specific tooth structures; iii) the use of both a top-down and bottom-up approaches to fabricated materials with properties similar to (or better than) of those of tooth structures; iv) the development of tools that are important for information extraction and manipulation of cellular events. If the approach is to use stem cells as the major strategy in creating a tooth, then novel bioinspired, instructive materials and engineering approaches that augment the migration of stem cells and/or progenitor cells should be considered

Given the complexities of an entire tooth organ, mathematical modeling, informatics and computational approaches are very important for the success of a project. Therefore, under c) computational sciences applicants should consider topics such as, but not be limited to: i) development of computerized modeling systems, computer-based design methods (e.g., the whole tooth shape, isolated tissues, scaffolds, property calculation, diffusion rate estimation, etc.), simulation methods and visualization software; ii) development of computational models for multiscale characterization in order to determine the controlling interfacial properties in the system (e.g., mineral/matrix, fibril/apatite, periodontal membrane/alveolar bone, etc.) and iii) development of software infrastructure that assists seamless integration between biology-driven projects and material science based approaches.

Applicants may wish to include as consultants NIDCR intramural scientists who have pioneered developmental and stem cell biology of the tooth in their laboratories.

3. Specialized Resources. The BTBBMS will provide Specialized Resource Facilities and Services. The lack of available facilities for cross-disciplinary experiments is often a barrier to productive scientific interactions. Demands on equipment, resources, and reagents in every scientific area are extremely high, and this demand prohibits ready access to investigators interested in expanding their studies into new areas of research. Specialized Resources dedicated to BTBBMS should be developed. Prioritization of the research projects supported through BTBBMS Specialized Resources will be an essential function of the BTBBMS leadership, and the mechanism to be employed for prioritization must be delineated by the applicants.

Milestones

All applications must include a specific section labeled “Milestones” for each year. Milestones should be annual, well-described, quantitative, and scientifically justified and not simply a restatement of the specific aims. These milestones will be used to judge the success of the proposed research on an individual-project basis. It is expected that the milestones will be adjusted annually at the award anniversary dates to incorporate the group's scientific accomplishments and progress and to reflect any recommendations of the Steering and Advisory Committees.

Internal Advisory Committee

Programs will be expected to have their own Internal Advisory Committee that includes experts outside the project. While a description of the Committee's activities should be included in the application, potential experts outside the project who would serve on the Internal Advisory Committee should not be named, contacted, or selected until an award has been made. Costs for activities of the Steering Committee should be included in the budget.

Progress Reviews, Milestones and Evaluations

The annual progress report will have two parts. The first will be the standard NIH progress report (Form 2590). The second will be a more specialized report that should be included as an attachment to the standard progress report and will go to the NIDCR Program Director. The content and format of this specialized report will be defined by the Project Scientist.

The NIDCR Program Director and Project Scientist will review the progress of the award annually to assure that satisfactory progress is being made in achieving the project objectives. During the first year of funding, and during subsequent years if deemed necessary by the Program Officer(s), reviews may be more frequent. The adherence of the awardee to any approved data sharing plan and intellectual property plans, which would be part of the Terms and Conditions of award (see Section VI. Award Administration Information) would also be reviewed annually. Should problems arise in the conduct of the study, the NIDCR Program Director may require that the awardee submit quarterly reports on technical progress and fiscal matters.

The awardees' yearly milestones will be provided to the NIDCR Program Director and the Steering Committee and Scientific Advisory Panel. Following the review of milestones, the NIDCR may recommend reducing or withholding funds for any project that substantially fails to meet its milestones.

An evaluation component and evaluation criteria will be developed in partnership with the Steering Committee, the Scientific Advisory Panel and the NIDCR program staff. The purpose of the evaluation is to monitor and assess the performance of the U54 BTBBMS awarded in achieving the goals of this RFA.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the U54 award mechanism.

The NIH (U54) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator(s) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". 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 (additional instructions below). Similarly for each Component a separate detail budget of the first year and the entire 5 year proposed period of support should be included.

2. Funds Available

The NIDCR anticipates committing approximately $5.0 M total costs in FY 2007 to fund 1 U54 award.  The award will consist of 3 Components: 1) the Organization and Management Component; 2) the Research Component; and 3) the Specialized Resources Component. Each Component will have one PI. The total project period for a U54 application submitted in response to this RFA may not exceed 5 years. Applicants should include travel funds in the budget for the annual site visit and annual meetings. An application exceeding a total cost of $5,000,000 per year will be returned to the investigator as non-responsive to the RFA.

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

Although the financial plans of the NIDCR provide support for this program, an award pursuant to this funding opportunity is contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

This RFA is a one-time solicitation, and plans for this initiative beyond the current funding opportunity are indefinite.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

Only the previous P20 recipients are eligible to apply.

NIDCR intramural scientists with expertise in tooth development and tooth stem cell biology are eligible as consultants.


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.

More than one PI, or multiple PIs, may be designated on the application.  Additional information on the implementation plans and policies and procedures to formally allow more than one PI on individual research awards can be found at http://grants.nih.gov/grants/multi_pi.  All PIs must be registered in the eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PI or multiple PI grant is the responsibility of the applicant organization and should be determined by the scientific goals of the project. Applications for multiple PI grants will require additional information, as outlined in the instructions below, and the NIH review criteria for approach, investigator and environment will be modified as indicated below. For example, a weak or inappropriate PI can have a negative effect on the review. If the multiple PI grant option is elected, a contact PI must be named, as described in the instructions below.  Multiple principal investigators on a project share the authority and responsibility for leading and directing the project, intellectually and logistically.  Each principal investigator is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of all required reports.

Multiple PIs may be located at the same institution or at different institutions and may request budget apportionment between the PIs (see supplementary instructions below).  For multiple organizations, a subcontract or consortium arrangement must be agreed on by the participating organizations, as described in special instructions below.

2. Cost Sharing or Matching

Cost sharing is not required.

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

3. Other-Special Eligibility Criteria

This is a limited competition and only the three P20 grantees can apply. Their grant number and affiliation are: 1 P20 DE017447-01 Univ. of Illinois at Chicago; 1 P20 DE017453-01 Brigham & Women's Hospital and; 1 P20 DE017460-01 Univ. of Southern California

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.

SUPPLEMENTARY INSTRUCTIONS:

1) Inclusion of Multiple PIs

Face page. Name of Principal Investigator (PI)

The PI is the individual(s) designated by the applicant organization to have the appropriate level of authority and responsibility to direct the program.  The applicant organization may designate multiple individuals as PIs who share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PI is responsible and accountable to the grantee organization or, as appropriate, to a collaborating institution, for the proper conduct of the project or program, including submission of all required reports.

When multiple PIs are proposed, use Face Page (Continued) page to provide items 3a-3h for all PIs. NIH requires one PI be designated as the “contact PI” for all communications between the PIs and the agency. The contact PI must meet the eligibility requirements for PI status in the same way as other PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PI may be changed during the project period. The contact PI should be listed in block 3 of Form Page 1 (the Face Page), with additional PIs listed on the Face Page (Continued). All PIs must be registered in the eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

Format Page 2. Key Personnel

When multiple PIs are proposed, list the Contact PI first, then all additional PIs in alphabetical order.  Then, list all Key Personnel, giving name and organization.

2) Budget(s):

The budget(s) should be presented in logical, discrete units for each section of the application using the standard PHS-398 form pages 4-5.

The budgets to be submitted should include:

a) A detailed composite budget for the entire U54 BTBBMS;
b) A separate budget for Administrative, Organizational Activities and Specialized Resources;
c) A separate budget for each individual subproject in the Research Component;

Additional pages for budget justification are to be used when necessary.

3) Research Plan

The following format is suggested for completing the “Research Plan” section (see pages 19 through 23 of the PHS 398 application brochure.) The application should be as concise as possible to ensure a thorough review.

a) Description of the vision and the strategies to implement that vision (not to exceed 5 pages)

This section should be used to present the overall vision for the BTBBMS. This summary should contain the long and short-term scientific objectives, specifically addressing how knowledge from the study of tooth biology will: i) inform the design of engineering approaches; ii) improve the development of tools needed to extract additional information, at various lengths of scale. This section should also summarize the organizational structure for the BTBBMS, by concisely defining subprojects in the Research Component, Specialized Resources, and their relationships to each other. In addition, relationships between the BTBBMS and other research, academic, and administrative units of the institution(s) (such as centers, institutes, departments) and the central administration should be described in this section. The description should serve as an overview of the U54 BTBBMS, with a more detailed description of each component to be presented in a later section.

b) Organization and Management (not to exceed 10 pages, including any organizational charts). A separate budget should be prepared and included for centralized administrative and organizational activities. The Organizational and Management Component should describe all of the infrastructure and decision-making needs of the U54 BTBBMS.

Appropriate for inclusion in this component would be (not necessarily in the following order):

c) Research Component (not to exceed 15 pages for each of the subprojects: a) cell and developmental biology; b) material and engineering sciences; and c) computational sciences.

Research Component will define the subprojects supporting the long-term goals of the U54, and are to be presented using the format of a traditional research project [Research Plan: Include Sections a-d (Instructions for PHS 398, Pages 15-17)]. The leader(s) of the Research Component will be responsible for ensuring that ongoing research subproject(s) are relevant to the U54 BTBBMS goals, and that the investigators and subprojects remain highly integrated with other ongoing U54 research. Research Component subprojects may rely on the support of the Specialized Resources. Each Research Component subproject should be described in sufficient detail to enable reviewers to judge the scientific merit from the written application (without need for additional information).

Following the description of the scientific goals, each subproject under the Research Component should summarize exactly how it integrates with the goals of the U54 BTBBMS, how it will directly support or impact clinical dentistry, and how it will communicate and complement the other subprojects. Describe in this section the relevance of the subproject to the primary theme of the U54 and the collaborations with investigators within the BTBBMS. Explicitly state which Specialized Resources will be used by this Research Component, and if possible, quantitate the anticipated usage of Specialized Resources in tabular format. This summary should not exceed 1-2 pages, which are included in the Research Component section.

d) Specialized Resources (not to exceed 10 pages each)

Specialized Resources may include laboratory facilities, equipment, and services. For each Specialized Resource, describe in detail the resource(s) that it will provide to the BTBBMS. In addition, describe its role in the overall functioning of the U54, including how each resource will enhance multidisciplinary research, and a description of the projects that will be supported by the Specialized Resource.

1. Using a Form PHS 398 Continuation Page, denote "Specialized Resource" and the Specialized Resource director's name. If there is to be more than one core component, prepare a separate section for each core (i.e., Specialized Resource A, Specialized Resource B, etc.).

2. For each Specialized Resource, describe the role of the Specialized Resource as a core to the U54 BTBBMS as a whole. Clearly present the facilities, resources, services, and professional skills that the core component provides.

3. To aid in the review, it is suggested that a table that shows the estimated or actual proportional use of this Specialized Resource by each project, be included in the application. Justify this core component by discussing ways in which these centralized services improve quality control, produce an economy of effort, and/or save overall costs compared to their inclusion as part of each project in the U54 BTBBMS.

4)  Section I.  Multiple PI Leadership Plan.

For applications designating multiple PIs, a new section titled Leadership Plan should be included. The governance and organizational structure of the overall research project (U54 BTBBMS) should be described, including communication plans, publications, intellectual property issues (Section VI. Award Administration Information), and procedures for resolving conflicts. The roles and shared administrative, technical, and scientific responsibilities for the project or program should be delineated for the PIs, including responsibilities for human subjects and animal studies as appropriate. For competing continuation applications, the application should state how the research will be enhanced by employing a multiple PI approach. This section should also address the governance and organizational structure for Research Components that have designated more than one PI.

5. Section J. Consortium/Contractual Arrangements: If multiple institutions are involved, the project will be administered through a traditional consortium/contractual arrangement, and the usual documentation is required.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A).

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): December 29, 2006
Application Receipt Date(s): January 29, 2007     
Peer Review Date(s): April, 2007
Earliest Anticipated Start Date(s): July, 2007

Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research

Name, address, and telephone number of the Principal Investigator

Names of other key personnel

Participating institutions

Number and title of this funding opportunity

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Lynn Mertens King, Ph.D.

Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
45 Center Drive, Rm 4AN 32F
Bethesda, MD  20892-6402
Voice: (301) 594-5006
FAX: (301) 480-8303
Email: Lynn.King@nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Appendix material should not be sent with the application, but applicants should await specific instructions in a later contact from the Scientific Review Administrator. Submit a signed, typewritten original of the application, including the checklist, and three 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).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Lynn Mertens King, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
45 Center Drive, Rm 4AN 32F
Bethesda, MD  20892-6402
Voice: (301) 594-5006
FAX: (301) 480-8303
Email: Lynn.King@NIH.gov

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 NIDCR. Incomplete and non-responsive applications will not be reviewed. If the application is not responsive to the RFA, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

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

6. Other Submission Requirements

It is recognized that the applications in response to this RFA will be longer and more complex than those of many other NIH applications. To ensure effective review, the application should be well organized as described in Section I. Funding Opportunity Description In particular, each of the required components identified earlier in the RFA Section I. Funding Opportunity Description and later on in Section IV. Application and Submission Information must be addressed.

For cooperative agreements, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI. Award Administration Information under
A. Cooperative Agreement Terms and Conditions of Award

Other submission requirements are described in detail below.

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.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may 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 expects 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 any 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 any 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.

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 NIDCR in accordance with the review criteria stated below.

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

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.

Receive a written critique.

Receive a second level of review by the National Dental and Craniofacial Research Council

The following will be considered in making funding decisions:

The NIDCR may select the most meritorious component from each application to form an outstanding National Center on Building a Tooth by Bridging Biology and Material Sciences (BTBBMS).

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application.

The overall U54 BTBBMS applications will be reviewed using the criteria listed below.

SIGNIFICANCE: What will be the impact of the BTBBMS on clinical dental care? Are the scientific objective(s) of the Research Component, Specialized Resources, appropriate and adequate to achieve the long-term goals of the BTBBMS?

APPROACH: Is the conceptual framework and the experimental design, methods and analyses proposed for each of the BTBBMS components sound and feasible? Do the individual subprojects listed under the Research Component interact appropriately with the other subprojects and the Specialized Resources? For applications designating multiple PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PIs?  Are the administrative plans for the management of the research appropriate, including plans to resolving conflicts?

INNOVATION: Are the experimental designs of the proposed research, focus on the design and building a functional tooth or tooth structures, original, novel, and innovative?

INVESTIGATOR(S): Are the U54 BTBBMS Director(s) and leadership appropriately trained and well suited to the organizational and scientific responsibilities of the BTBBMS? Is there evidence that U54 BTBBMS participants are committed to productive, multidisciplinary interactions? Are the principal investigator(s) and key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level(s) of the principal investigator(s) and other researchers? Do the principal investigator(s) and investigative team bring complementary and integrated expertise to the project?

ENVIRONMENT: Is there evidence of significant commitment of the institution(s) to fulfilling the objectives of the U54 BTBBMS? Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features in the scientific environment?

In addition, each U54 BTBBMS component will be reviewed using the following criteria:

1) Organization and Management

Is the organizational, scientific, and operational framework reasonable, well-integrated, and appropriate to the aims of the U54 BTBBMS? Does the U54 BTBBMS employ novel approaches or methods for facilitating scientific interaction? Are the U54 BTBBMS Director(s) and leadership appropriately trained and well suited to the organizational and scientific responsibilities associated with this project? Is there sufficient oversight and monitoring of Research Components and Specialized Resources? Is there evidence of significant commitment of the institution(s) to fulfilling the objectives of the U54 BTBBMS? If collaborative arrangements are proposed, is there a convincing demonstration that these interactions will be consistent enough to meet the needs of the U54 BTBBMS? For applications designating multiple PIs, does the U54 BTBBMS governance plan ensure that there will be sufficient coordination and communication among the PIs? 

2) Research Component

The five criteria to be used to evaluate the scientific and technical merit of each individual subproject under the Research Component are listed below:

SIGNIFICANCE: Does the Research Component address an important research problem related to building a functional tooth using biological and engineering principles? Will the research have an impact on clinical dental care? Does the scientific merit and experimental design of the Research Project adequately addresses issues of substantive importance?

APPROACH: Are the conceptual research framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the goals of the project and to the U54 BTBBMS as a whole? Does the applicant acknowledge potential problem areas and consider alternative translational approaches? Is there clear evidence of significant multidisciplinary basic and clinical interactions in the conception, design, and proposed implementation of the project?  Does the Leadership Plan ensure that there will be sufficient coordination and communication among the subproject PIs?

INNOVATION: Do the subprojects listed under the Research Component develop new methodologies or technologies that can advance the development or improvement of new tools? Is the experimental design of sufficient originality, novelty, and innovativeness to make it highly relevant to the overall goals and objectives of the U54 BTBBMS?

INVESTIGATORS: Are the investigator(s) appropriately qualified with demonstrated competence to conduct the proposed research? Is the proposed work appropriate to the experience level of the investigators? Are the proposed time commitments for all key laboratory and clinical researchers reasonable and adequately associated with the project?

ENVIRONMENT: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features in the scientific environment or reach out to useful collaborative arrangements? Is there evidence of adequate institutional support?

3) Specialized Resources

Is each Specialized Resource essential for the conduct of U54 BTBBMS? Is the Specialized Resource utilized by more than one Research Component? Is the access to, and distribution of, Specialized Resources focused on meeting the goals of the U54 BTBBMS? Are the proposed managers of Specialized Resources adequately qualified to conduct high quality, reliable resource operations? Are the requested budgets appropriate to conduct each resource operation?

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 of all components when applicable:

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

The reasonableness of any data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor any proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring any approved data sharing plan consistent with the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

All awards made under this RFA are subject to the Final NIH Statement on Sharing Research Data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html) and the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources (http://www.ott.nih.gov/policy/rt_guide_final.html). This document also defines terms, parties, responsibilities, prescribes the order of disposition of rights, prescribes a chronology of reporting requirements, and delineates the basis for and extent of government actions to retain rights. Patent rights clauses may be found at 37 CFR Part 401.14 and are accessible from the Interagency Edison web page, http://www.iedison.gov. It is expected that research resources generated through the award will be shared by awardees according to these guidelines. Any plans for the development of resources for use by the biomedical community will have the appropriate timelines and milestones. NIDCR program staff will evaluate the compliance with any sharing plan and scientific progress in the non-competing progress report (Form 2590); such compliance will be a criterion for continued funding of the award.  

2.D. Sharing Research Resources

NIH policy expects 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.

The adequacy of any resources sharing plan will be considered by NIDCR Program staff when making recommendations about funding applications. Program staff may negotiate modifications of any data and resource sharing plans with the awardee before recommending funding of an application. The final version of any data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of any such 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.

Dissemination of Research Results

This initiative encourages investigators to facilitate translating effective interventions and tools into practice. As part of the NIDCR's commitment to the rapid translation of research evidence into practice, applicants should include explicit plans to disseminate research results into practice.

Guidance for Preparation of an Intellectual Property Management Plan.

Intellectual property management plans may be submitted after peer review, following a just-in-time model; it is not necessary to include any final plan approved by all parties in the grant application, but any final, approved plans will be expected before the application can be awarded. NIDCR program staff will consider the adequacy of any  plans in determining whether to recommend funding. Any approved plans would become a condition of the grant award and Progress Reports would contain information on activities for the sharing of research resources and intellectual property.

In the development of any research resource sharing and intellectual property management plans, applicants should confer with their institutions' office(s) responsible for handling technology transfer related matters and/or sponsored research. If applicants or their representatives require additional guidance in preparing such plans, they are encouraged to make further inquiries to the appropriate contacts listed above for such matters.

The intellectual property management plans are expected under this RFA. Such plans should address the following components:

1. Invention Disclosure and Patent Management

The Bayh-Dole Act and subsequent amendments addressing “Rights to Inventions Made by Nonprofit Organizations and Small Business Firms”, as codified in 37 CFR 401, confers rights and responsibilities for inventions arising from federally funded grants. As part of any Intellectual Property (IP) Management Plan, applicants should define procedures for documenting and patenting new inventions arising from the work funded by this RFA. These should include:

Record Keeping- To document discoveries made in the course of the projects. Applicants should describe institution policies for maintaining proper records.

Invention Disclosure- The IP Management Plan should identify the institutional mechanism for reporting inventions, specifying the responsible office and forms. This plan should include provisions to establish appropriate invention disclosures prior to publication or presentation of project data.

Patenting - Any IP management plan should include the institutional process and timetable for deciding whether to retain title on inventions, filing U.S. and foreign patent applications, and notifying NIDCR. Recipients of federal funds must disclose each new invention to the funding agency within two months after disclosure in writing to the institution under the Bayh-Dole Act. Describe institutional policies for patent searches and basis for filing provisional patents.

Patent Reporting- Summarize the institutional mechanism for providing patent and licensing information to the appropriate government agency, including:

• Office of Policy for Extramural Research Administration (OPERA) notification of any invention developed under funding for this project and provision of a non-exclusive, nontransferable, irrevocable, paid-up license.
• Annual Invention Utilization Reports documenting the status of licensing and development, including date of first commercial sale or use and gross royalties received. Reporting requirements can be satisfied by electronic data entry into the Interagency Edison system.
• Final Invention Statement (form HHS 568) should be sent to NIDCR prior to grant closeout.

2. Licensing and Commercialization

Any IP management plan should identify the institutional office responsible for technology licensing and outline potential strategies for licensing the prototype device for commercialization. Provisions for dissemination and licensing may include:

Material Transfer Agreement- To encourage further research and development by not-for-profit institutions, awardees should disseminate information and reagents developed in this grant consistent with the NIH Research Tools Policy ( http://grants.nih.gov/grants/intell-property_64FR72090.pdf), such as through the Simple Letter Agreement (SLA).

Option- A limited time option may be granted to an existing or potential partner during the period of development, leading to negotiation of a subsequent license for commercial purposes to the extent consistent with NIH policies, e.g., see http://iedison.gov/Edison/sponsored.html.

Non-exclusive License

Exclusive License

Company spin-outs

Other novel commercialization strategies

3. Inter-Institutional Agreement

If investigators in the grant application are collaborators from multiple independent institutions, any IP Management Plan should include an inter-institutional agreement for coordinating patent prosecution, licensing, and for sharing royalties amongst institutions and investigators. This agreement should specify the lead office for patenting and licensing inventions that arise from the collaboration. A uniform policy on record keeping and reporting should also be presented.

This guidance is provided to assist applicants in preparing any intellectual property management plans to encourage partnerships with industry in order to meet certain programmatic objectives and goals of particular funding announcements. Applicants are encouraged to use their own discretion to independently develop and submit their own plans for consideration.

3. Anticipated Announcement and Award Dates

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/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 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. The NIDCR may select the most meritorious component from each application to form an outstanding National Center on Building a Tooth by Bridging Biology and Material Sciences (BTBBMS).  

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).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U54), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Principal Investigator Rights and Responsibilities

The PIs will coordinate project activities scientifically and administratively at the awardee institution, including research design and protocol development, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications.

The PIs will have the primary responsibility for all the components of the U54 award Building a Tooth by Bridging Biology and Material Sciences (BTBBMS). The PIs will agree to accept close coordination, cooperation, and participation of NIDCR staff in those aspects of scientific and technical management of the project as described below. Specifically, the PIs will:

Determine experimental approaches, design protocols, set project milestones, and conduct experiments

Propose protocol modifications as required

Analyze and interpret research data

Provide goals for assay optimization, screening throughput, quality, and cost to the NIDCR Program Director as requested, usually at the outset of the award and in annual progress reports, but also at other times if requested

Release data according to any approved plans for timely sharing of research resources and data generated through the award, and publish results, as agreed upon by the Steering Committee

Establish an Internal Advisory Committee to provide scientific and administrative oversight. The Internal Advisory Committee will be composed of the lead institute personnel, external scientific advisors and other technical or research personnel. The committee is expected to meet at least twice a year. Minutes of these meetings will be made available to NIDCR staff upon request

Serve on the Steering Committee or appoint an appropriate designee to do so

Provide information to the NIDCR Program Director and Project Scientist concerning progress by submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and Scientific Advisory Panel

Accept and implement all scientific, practical, and policy decisions, common guidelines and procedures approved by the Steering Committee and Scientific Advisory Panel

Share facilities, research resources, tools, and data of interest to those facilities with other awardees consistent with the terms and conditions of award and as directed by the Steering and Advisory Committees;

Share standardized information on new developments and/or methods for solving obstacles with the investigators funded through this initiative and with the NIDCR staff

Prepare for annual administrative site visits by NIDCR staff

Upon completion of the project put all study design materials and procedure manuals into the public domain and/or make them available to other investigators, according to any approved plan for making data and materials available to the scientific community and the NIDCR, for the conduct of research at no charge other than the costs of reproduction and distribution.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

NIDCR Staff Responsibilities: The Institute will designate a Program Scientist who will have substantial scientific-programmatic involvement above and beyond normal program stewardship during contact of this activity. The Project Scientist will:

Help coordinate collaborative research efforts in the subprojects of the Research Component

Review and comment on critical stages in the subprojects of the Research Component research program before subsequent stages are implemented

Assist in the interaction between the awardee and investigators at other institutions

Be a voting member of the Steering Committee and its subcommittees

Help the Steering Committee develop and draft operating policies and policies addressing recurring situations that require coordinated action

May consult with other NIDCR and NIH staff as well as non-NIH experts in the field in order to carry out these responsibilities.

In addition, the NIDCR will designate a Program Director and a Grants Management Specialist to provide administrative oversight of the cooperative agreement.

The NIDCR Program Director will:

Be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice as the NIH program official.

Carry out continuous review of all activities to ensure objectives are being met.

Review the progress of the 3 (Organizational Component, Research Component and Specialized Resources  Component) U54 BTBBMS Components for compliance with operating policies developed by the Steering Committee, and may recommend to the NIDCR to withhold support, suspend, or terminate a subproject for lack of scientific progress or failure to adhere to policies established by the Steering Committee.

Have the option to recommend, with the advice of the Steering Committee and Scientific Advisory Panel, the withholding, reduction or termination of support for any subproject under the 3 U54 Components that substantially fails to achieve its goals according to the milestones agreed to at the time of the award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award

Retain the option to recommend additional research endeavors within the constraints of the approved research and negotiated budget and the scope of RFA-DE-07-009.

Support or other involvement of industry or any other collaborators in any study performed by the awardees may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following approval of the NIDCR Program Director. The NIDCR reserves the right to require the transfer of appropriate reagents, tools and pertinent data that are generated as the result of participation in research supported under these awards to an eligible third party, in order to advance the research. Collaborators supported under these awards must be informed of this right.

2.A.3. Collaborative Responsibilities

Steering Committee: The NIDCR Program Scientist and PIs of the U54 funded under this RFA will be responsible for forming a Steering Committee as defined below. The Steering Committee will act as the main governing board that will review the progress of the research activities, develop collaborative protocols, identify technological impediments to the progress, select strategies to surmount them, and identify opportunities for sharing techniques and tools developed within each individual project. The Steering Committee will:

Advise NIDCR Program Staff of scientific developments and opportunities that may enhance the goals of the program.

Help to develop uniform procedures and policies, for the governance of the awards under RFA-DE-07-009.

Serve as a venue for coordination on improving the state of the art, for example by reporting progress, disseminating best practices and collectively evaluating new procedures, resources, and technologies.

The Steering committee will be composed of the PIs of the 3 Components funded through RFA-DE-07-009, and the NIDCR Program Scientist. The PI of each Component will have one vote and the NIDCR Program Scientist will have one vote. The Steering Committee may, as it deems necessary, invite additional, non-voting scientific advisors to meetings at which research priorities and opportunities are discussed.

There will be two meetings of the Steering Committee in the first year and one meeting per year in the following years. The first meeting of the PIs funded under this RFA will be a Planning Meeting in the Bethesda, MD area soon after awards are issued. At the planning Meeting the Steering Committee will be formed. At the first Steering Committee meeting the members may: (a) draft a charter to detail policies and procedures and develop a process for monitoring compliance with the policies and procedures and for recommending that the NIDCR Program Director act on evidence of non-compliance with Steering Committee policies; (b) agree upon the terms of the charter; and (c) discuss the approaches that were proposed in the project applications and any relevant new information, and set initial priorities for the projects to be pursued.

Scientific Advisory Panel

The Scientific Advisory Panel (SAP) will be appointed by NIDCR and be responsible for reviewing and evaluating the progress of the awardees toward meeting their individual and collective goals. The SAP will provide recommendations to the Director, NIDCR, about continued support of the individual subprojects and the group of subprojects awarded under RFA-DE-07-009. The Advisory Panel will be composed of three to four senior scientists with relevant expertise. The membership of the Scientific Advisory Panel may be enlarged permanently, or on an ad hoc basis, as needed. The Scientific Advisory Panel will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the Scientific Advisory Panel members to interact directly with the awardees. Annually, the Scientific Advisory Panel will make recommendations regarding progress of the individual and collective group of projects and present advice about changes, if any, to the NIDCR Director.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

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. The annual progress report for the U54 award will use the standard 2590 form as well as supplementary information that will be more extensive. Additional information in the progress report will include both the progress made in the project as well as the relationship between the awardee and collaborators. Details of the progress report are spelled out in the notice of grant award and in the Terms and Conditions section of this RFA.

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:

Eleni Kousvelari, DDS, D.Sc.
Acting Director,
Center for Biotechnology and Innovation
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4N 24F
Bethesda, MD  20892-6402
Telephone:  (301) 594-2427
FAX:  (301) 480-8318
Email: kousvelari@de45.nidr.nih.gov

2. Peer Review Contacts:

Lynn Mertens King, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
45 Center Drive, Rm 4AN 32F
Bethesda, MD  20892-6402
Voice: (301) 594-5006
FAX: (301) 480-8303
Email: Lynn.King@NIH.gov

3. Financial or Grants Management Contacts:

Mary Daley, Chief
Grants Management Branch,
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
Natcher Bldg. 45, Room 4AN-44B
Bethesda, MD  20892
Telephone: (301) 594-4808
FAX: (301) 480-3562
Email: daleym@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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.

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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This 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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