Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)
National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Dental and Craniofacial Research (NIDCR)

Funding Opportunity Title
Defining Lineage Plasticity and Endogenous Regeneration Capacity of Dental, Oral, and Craniofacial Tissues (R01 Clinical Trial Not Allowed)
Activity Code
R01 Research Project Grant
Announcement Type

New

Related Notices
July 26, 2019- Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128

August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137

Funding Opportunity Announcement (FOA) Number
RFA-DE-20-006
Companion Funding Opportunity

RFA-DE-20-007, R21 Exploratory/Developmental Grant

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.121

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage studies that will interrogate the capacity of cells residing in the postnatal Dental, Oral, and Craniofacial tissues to acquire developmental plasticity to undergo lineage reprogramming in vivo in response to injury and other types of environmental stress, and to generate functionally-competent cells of alternative lineage(s). The end goal of this initiative is to develop approaches for capitalizing on this developmental plasticity for obtaining needed cells to promote endogenous regeneration of Dental, Oral, and Craniofacial tissues affected by disease or injury for achieving the goals of regenerative medicine. This Initiative will build a basic science foundation for developing clinically relevant, minimally invasive strategies for overcoming limitations of the currently available regenerative medicine methodologies.

Key Dates

Posted Date

March 13, 2020

Open Date (Earliest Submission Date)
June 08, 2020
Letter of Intent Due Date(s)

June 08, 2020

Application Due Date(s)

July 8, 2020 No late applications will be accepted for this Funding Opportunity Announcement

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

July 31, 2020

Scientific Merit Review

October 2020

Advisory Council Review

January 2021

Earliest Start Date

April 2021

Expiration Date
August 01, 2020
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Research Objectives

Regenerative medicine strives to heal and functionally and structurally restore tissues and organs compromised by disease or injury. Advances are continually being made in this area; however, one of significant remaining bottlenecks impeding progress has been an inadequate supply of cells for generation of new tissues. Currently available methods often rely on injection into tissues of in vitro expanded heterogeneous stem and progenitor cell populations or in vitro differentiated progeny of pluripotent cell lines. While there have been promising developments in these areas, many challenges remain, including insufficient characterization of stem/progenitor cells as to their capacity to generate functional progeny, low numbers of cells available for building new tissues as well as poor function, survival and integration of the injected cells with host tissues. The present initiative addresses these obstacles, through promoting endogenous healing and regeneration of Dental, Oral, and Craniofacial tissues, which avoids injection of exogenously manipulated cells. The immediate purpose of this Funding Opportunity Announcement (FOA) is to build a basic science foundation for understanding mechanisms of endogenous lineage reprogramming of Dental, Oral, and Craniofacial tissues. To this end, this FOA will support studies that interrogate the capacity of cells residing in the postnatal Dental, Oral, and Craniofacial tissues to acquire developmental plasticity to undergo lineage reprogramming in vivo in response to injury and other types of environmental stress, and to generate functionally-competent cells of alternative lineage(s) that can be induced to participate in endogenous tissue regeneration. The long-term goal is to develop practical approaches for capitalizing on this developmental plasticity for obtaining needed cells for building new Dental, Oral, and Craniofacial tissues and derive clinically relevant minimally invasive strategies for overcoming limitations of currently available regenerative medicine methodologies.

Background

The capacity of DOC tissues to undergo endogenous healing and regeneration remains largely unexplored. It varies widely among species, types of Dental, Oral, and Craniofacial tissues, and the extent of incurred injury. For example, following cuts and abrasions, normal human oral mucosa heals better and faster than most other tissues in the body. On the other hand, oral cancer chemotherapy and radiation commonly result in nonhealing lesions of oral mucosa - oral mucositis - a condition responsible for severe patient morbidity. Human dental and salivary gland tissues do not exhibit significant regenerative capacity, while rodent incisors regenerate throughout life. Human craniofacial bone and skeletal muscle regenerate small defects but fail to do so when the defect exceeds critical size and/or in the presence of infection and chronic inflammation. While mechanisms of differential regenerative capacity of tissues are complex and still poorly understood, it is recognized that the availability of stem/progenitor cells to generate new tissues is one of the key factors needed for successful regeneration. Traditionally, in mammals the developmental progression from stem/progenitor cells to fully differentiated functional cells has been viewed as a unidirectional and terminal process, but recent advances beginning with a derivation of induced pluripotent stem cells and a discovery of cellular reprogramming, put the universality of this simple paradigm into question. In fact, multiple examples of naturally occurring in vivo reprogramming of differentiated cells into stem/progenitor state following injury and/or inflammatory stress have been described. The best-studied example of this phenomenon is found in mammalian small intestine, but similar findings have been described in lung, skin, pancreas, liver, brain and heart, tooth and bone. Alternatively, and/or in addition, lineage reprogramming in vivo can be induced by targeted gene transfer to deliver to cells genes coding for master tissue-specific genetic and epigenetic regulators via viral vectors or other gene transfer technologies. Accomplishing controlled and safe in vivo lineage reprogramming would provide minimally invasive means for generating needed cell sources. Moreover, such reprogrammed cells are likely to have multiple advantages over injected in vitro-manipulated cells, because survival, function and integration of in vivo reprogrammed cells with host tissues would be supported by endogenous Dental, Oral, and Craniofacial stem cells niches. In these niches, accessory somatic cells, soluble signaling mediators and extracellular matrices would provide guidance cues to stem/progenitor cells to generate new tissues. Overall, achieving the goals of this initiative will create unprecedented opportunities for healing and regeneration of Dental, Oral, and Craniofacial tissues.

Gaps and Opportunities

Significant knowledge gaps currently exist in understanding of the mechanisms of inherent and induced lineage plasticity of mammalian Dental, Oral, and Craniofacial tissues and the role of stem cells niches and other signals, including immune system-mediated signals, in controlling this plasticity. Overcoming these knowledge gaps is likely to create a new generation of approaches - autotherapies - that take advantage of endogenous healing and regeneration capacity of Dental, Oral, and Craniofacial tissues to restore their structure and function. More specifically, these autotherapies will target endogenous Dental, Oral, and Craniofacial stem/progenitor cell niches and differentiated somatic cells for lineage reprogramming for generating new cells for re-building Dental, Oral, and Craniofacial tissues and restoring normal tissue homeostasis. Currently, NIDCR portfolio does not contain projects directly focusing on in vivo lineage reprogramming. However, recent findings in the field have provided promising results suggestive of inherent lineage plasticity of Dental, Oral, and Craniofacial tissues. Further, recent emergence of new experimental tools and approaches for interrogation lineage plasticity suggests the timeliness of this effort. Several NIH Institutes including NIDDK, NIAMS, NHLBI and NINDS, currently support such projects as applied to those Institutes' missions. The proposed NIDCR initiative is synergistic with this existing trans-NIH effort. Moreover, a Keystone Symposium titled "Cellular Plasticity: Reprogramming, Regeneration and Metaplasia", was held in January 2019 and another Keystone Symposium titled "Tissue Plasticity: Preservation and Alteration of Cellular Identity" is being planned for October 2020. These conferences are indicative of a robust interest of the scientific community, and of a critical mass of knowledge being generated in this new field. Given the strong interest of NIDCR in advancing Dental, Oral, and Craniofacial tissue regeneration, it is important for the Institute to join this effort. To achieve maximum results, this initiative will highly encourage collaborations of Dental, Oral, and Craniofacial tissue regeneration experts with investigators exploring lineage plasticity and reprogramming of other tissues in the body.

Scope and Areas of Interest

The long-term goal of this FOA within an umbrella of NIDCR 2030 Theme Autotherapies, is to develop practical approaches for capitalizing on developmental plasticity of Dental, Oral, and Craniofacial tissues for their healing and regeneration. To achieve these goals, it will be necessary to build a strong basic science knowledge base to define the capacity of Dental, Oral, and Craniofacial cells to undergo in vivo lineage reprogramming in response to injury and other types of environmental stress, elucidate molecular and cellular mechanisms, identify signaling pathways and mediators of this reprogramming, and develop approaches for optimizing safety and efficiency of reprogramming in appropriate animal models. While this FOA is focused on lineage reprogramming in vivo, employment of in vitro model systems, would be within the scope of this FOA, as long as the proposed experimental plans address questions relevant to reprogramming in vivo. Employment of tools and technologies such as, single cell-based analyses, including single cell transcriptomics, epigenomics and proteomics; bioinformatics, machine learning or systems biology; tissue organoids or tissue/organ on chips; bioengineering, genome-editing or gene transfer; high-resolution real-time imaging, among others are expected. The specific areas of interest include but are not limited to those listed below:

  • Elucidation of the molecular and cellular mechanisms and the nature of signaling mediators and pathways of Dental, Oral, and Craniofacial cell lineage reprogramming
  • Investigation of the innate and adaptive immune system- mediated mechanisms of Dental, Oral, and Craniofacial cell lineage reprogramming
  • Investigation of molecular and cellular components and modes of interactions within Dental, Oral, and Craniofacial stem cell niches that mediate lineage reprogramming
  • Elucidation of developmental relationships and dynamic lineage transitions among cells comprising Dental, Oral, and Craniofacial stem cell niches that underlie tissue regeneration in response to injury or environmental stress
  • Derivation of new and refining existing approaches, including bioengineering approaches, for targeted manipulation of in vivo tissue microenvironment to achieve efficient and safe Dental, Oral, and Craniofacial cell reprogramming
  • Derivation of new and refining existing animal models, including mouse genetic models to serve as experimental systems for studies of Dental, Oral, and Craniofacial cell lineage reprogramming
  • Derivation of in vitro systems to serve as experimental systems for studies of Dental, Oral, and Craniofacial tissue lineage reprogramming
  • Development of cell type-specific biomarkers of Dental, Oral, and Craniofacial cell lineage reprogramming
  • Development and refining strategies for targeted gene manipulations of defined cell populations to allow interrogation of Dental, Oral, and Craniofacial cell plasticity
  • Derivation of functional assays and readouts for monitoring Dental, Oral, and Craniofacial cell lineage reprogramming

    The following areas of focus for research projects are not responsive to this FOA:
  • Projects employing single cell analysis, such as transcriptomics, epigenomics and proteomics, but not directly related to investigation of Dental, Oral, and Craniofacial cell lineage plasticity
  • Projects that focus on developing and/or utilizing tools and technologies listed in Specific Areas of Interest above, but not directly related to investigation of Dental, Oral, and Craniofacial cell lineage plasticity

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDCR intends to commit $3M total costs in FY 2021 to fund 5-8 awards solicited from RFA-DE-20-006 and RFA-DE-20-007.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • U.S. Territory or Possession
Other
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

 

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guideexcept where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

 

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Dr. Yasaman Shirazi
Telephone: 301-594-5593
Email: shiraziy@mail.nih.gov

Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed
Instructions for Application Submission
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.

This FOA encourages collaborations among investigators already involved in studies of endogenous lineage plasticity and reprogramming of Dental, Oral, and Craniofacial and other types of tissues with those who are only entering this field. It requires that expertise and prior experience in studying lineage plasticity and reprogramming be present on the team.For those investigators who are only entering the field, multi-PI applications are highly encouraged. Additionally, if one or more types of single-cell analyses are involved in the project, bioinformatics expertise on the team is required.

 

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

The Research Plan is required to address the following topics:

  • How the scope of the proposed project directly addresses endogenous lineage reprogramming of Dental, Oral and Craniofacial cells
  • How the proposed Specific Aims will allow achieving the goals of the proposed project
  • What existing or to be developed in vivo or/and in vitro model systems, including injury model system, will be employed
  • Which functional assays and readouts will be used to detect lineage reprogramming events
  • Which strategies will be used for detecting, monitoring and tracing lineage reprograming eventsin the heterogeneous cell populations of Dental, Oral, and Craniofacial tissues and organs
  • Which cell type specific biomarkers will be used for detecting lineage transitions
  • Which approaches will be employed for analyzing lineage plasticity of Dental, Oral, and Craniofacial cells on a single-cell level
  • How endogenous Dental, Oral, and Craniofacial tissue regeneration will be tested and monitored
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, are required to address a Data Sharing Plan.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
 

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIDCR, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

 

Does the project address an important problem or a critical barrier to progress in the field Is the prior research that serves as the key support for the proposed project rigorous If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

  • Does the investigative team include researchers who have expertise and prior experiencein studying lineage plasticity and reprogramming of Dental, Oral, and Craniofacial or other types of tissues?
  • If one or more types of single-cell analyses are involved in the project, is bioinformatics expertise on board and readily available?

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

  • Does the project address mechanistic aspects of Dental, Oral, and Craniofacial cell lineage reprogramming?
  • Are proposed in vivo and/or in vitro models appropriate for achieving ?the? goals of Specific Aims?
  • Are functional assays and readouts appropriate to monitor Dental, Oral, and Craniofacial lineage reprogramming and tissue regeneration?
  • Are appropriate biomarkers to be used for detecting lineage transitions defined?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

 

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

 

For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

Not applicable

 

Not applicable

 

Not applicable

Additional Review Considerations
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

 

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

 

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group convened by NIDCR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:
  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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.Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award
Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Scientific/Research Contact(s)

Nadya Lumelsky, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-7703
Email:nadyal@nidcr.nih.gov

Peer Review Contact(s)

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: yasaman.shirazi@nih.gov

Financial/Grants Management Contact(s)

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email:rutbergd@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Authority and Regulations
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 Part 52 and 45 CFR Part 75.
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