Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed)

Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). Supports research to identify and validate genetic variants linked to congenital anomalies, aiming to enhance understanding and potential interventions.

PAR-25-185: Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Dental and Craniofacial Research ( NIDCR ) Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs ( ORIP ) Funding Opportunity Title Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed) R01 Research Project Grant March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose Rapid advances in genotyping and next generation sequencing technologies have led to the identification of genetic variants that are associated with a wide variety of congenital defects including structural congenital anomalies (SCAs), intellectual developmental disabilities (IDDs) and inborn errors of metabolism (IEMs).

Large quantities of genomic data collected from pediatric congenital anomalies cohorts are available to the research community through several databases such as the Database of Genotypes and Phenotypes (dbGaP), the Gabriella Miller Kids First Data Resource Portal, the European Genome-Phenome Archive and Clinical Genome Resource (ClinGen).

The purpose of this initiative is to promote the screening, functional validation and characterization of congenital anomaly-associated genetic variants identified through public facing databases and individual efforts using in-silico tools, appropriate animal models, in vitro systems or multi-pronged approaches.

This initiative addresses a challenging gap between identifying sequence variations of potential interest and recognizing which of those variations have functional effects on the phenotype of interest. Funding Opportunity Goal(s) To conduct and support laboratory research, clinical trials, and studies with people that explore health processes.

NICHD researchers examine growth and development, biologic and reproductive functions, behavior patterns, and population dynamics to protect and maintain the health of all people. To examine the impact of disabilities, diseases, and defects on the lives of individuals. With this information, the NICHD hopes to restore, increase, and maximize the capabilities of people affected by disease and injury.

To sponsor training programs for scientists, doctors, and researchers to ensure that NICHD research can continue. By training these professionals in the latest research methods and technologies, the NICHD will be able to conduct its research and make health research progress until all children, adults, families, and populations enjoy good health.

The mission of the NICHD is to ensure that every person is born healthy and wanted, that women suffer no harmful effects from reproductive processes, and that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability, and to ensure the health, productivity, independence, and well-being of all people through optimal rehabilitation.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

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.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Purpose/Research Objectives Rapid advances in genotyping and next generation sequencing technologies have led to the identification of genetic variants that are associated with a wide variety of congenital defects including structural congenital anomalies (SCAs), intellectual developmental disabilities (IDDs) and inborn errors of metabolism (IEMs).

The purpose of this initiative is to promote the screening, functional validation and characterization of congenital anomalies-associated genetic variants identified through public facing databases and individual efforts using in-silico tools, appropriate animal models, in vitro systems or multi-pronged approaches.

The ultimate goal is to enhance the translation of basic knowledge gained from functional genomic approaches into the development of new, innovative, and efficacious strategies for the molecular diagnosis, treatment, and prevention of human birth defects.

Annually, almost five percent of all live births in the United States (more than 180,000 babies) involve babies born with congenital anomalies when broadly defined to include structural, functional, and metabolic abnormalities. Congenital anomalies are the leading cause of death in children within the first year of life and account for half of all pediatric hospitalizations.

Congenital anomalies have a great impact on public health, socioeconomics, and family life. The genomic revolution holds promise for enabling the discovery of effective and targeted therapies based on the underlying genetic classification of conditions – the basis for precision medicine.

Studies of developmental biology are revealing the underlying genetic networks essential to cell/tissue differentiation, morphogenesis, organogenesis, as well as functions of cells and cellular organelles. Disruptions in these fundamental developmental processes result in congenital anomalies.

The combined efforts of basic scientists studying the genetic networks and physician scientists sequencing patient cohorts together place the field of congenital anomalies research on the verge of major advances. The NIH has made significant investment in genomic studies and technologies to identify DNA sequence variations associated with a wide variety of congenital anomalies.

Among others, the Gabriella Miller Kids First Pediatric Research Program ( Kids First ), the Center for Mendelian Genomics ( CMG ), Pediatric Cardiac Genomics Consortium ( PCGC ), Deciphering Developmental Disorders ( DDD ) and the Undiagnosed Disease Network ( UDN ) are generating large-scale clinical and genetic data from patients and their families with syndromic and organ-specific developmental disorders.

Data generated through whole genome sequencing, SNP and SV analysis, and whole-exome sequencing are available to the research community through several databases such as the Database of Genotypes and Phenotypes ( dbGaP ), the Kids First Data Resource Portal , the European Genome-phenome Archive and ClinVar .

Despite an explosion of data resources, researchers face a challenging gap between identifying congenital anomaly-associated sequence variations and recognizing which of these variations have functional effects on the phenotype of interest.

In order to pursue mechanistic studies of how specific genetic variants affect developmental pathways and gene networks leading to the observed phenotype, researchers must have effective methods to screen potential variants to identify the causal ones.

Faster, less expensive, and more accurate gene-to-function screens are critical for accelerating the translation of genomic findings into greater understanding of human congenital anomalies.

This initiative encourages screening and functional validation of genomic variants associated with congenital anomalies and invites grant applications proposing to identify and prioritize genomic variants through in-silico analyses and/or cell-based assays, and followed by functional validation and deep mechanistic studies of causal variants in appropriate model systems.

Criteria for responsive applications: Applicants may propose non-hypothesis driven screening of variants to establish association with congenital anomalies under investigation, or hypothesis-driven mechanistic studies to generate critical information on how variant functions affect the disease phenotypes, or a combination of both types of studies.

Genomic variants may be selected from those available through public databases or identified via individual/group efforts such as ClinGen Expert Curation Panels. Genomic variants must be statistically associated with the congenital anomaly under investigation. Genomic variants may affect coding and/or non-coding regions.

Genomic variations including, but not limited to single base pair substitutions, copy number variations (insertions or deletions) and chromosomal rearrangements can be investigated.

Applicants are encouraged to use available genomic, gene expression and phenotypic databases and resources, such as the International Genome Sample Resource- IGSR , the Encyclopedia of DNA Elements- ENCODE data portal , the Gene Expression Omnibus- GEO data resource, Genotype-Tissue Expression ( GTEx ) - database, model organism databases, and appropriate bioinformatics tools for variant selection.

Variant selection criteria may include, but are not limited to the following categories: Variants prioritized based on existing clinical phenotyping data. Variants selected through functional prediction or variant interpretation tools (e.g. CiviC, Open Cravat).

Variants known to be associated with gene expression patterns in relevant tissue(s) and cell types that could reasonably be connected to normal biology and the disorder in question. Variants that currently lack functional annotation and need improved and/or high? throughput functional assays to establish a connection with the human phenotype of interest.

Novel variants associated with functionally annotated genes but lacking an established connection with the human phenotype in question. Variants known to be associated with epigenomic changes such as DNA methylation, histone modifications or DNase I hypersensitivity occurring in disease relevant cell types and potentially influencing gene regulation involved in the trait of interest.

Novel and/or high throughput screening strategies to validate genomic variants may be based on: Model organisms including but not limited to Drosophila , C. elegans , Xenopus , zebrafish, chick, mouse, or rat. In vitro model systems include, but are not limited to, organoids, and patient-derived or genome engineered induced pluripotent stem cells and their differentiated derivatives of defined genotype.

A combination of in vitro and in vivo model systems (cell or tissue-based culture systems). In order to determine the optimal model systems best suited to study human conditions of interest, the investigators are encouraged to use the existing resources for animal models or in vitro systems. These include, but are not limited to, the database of Drosophila Genes and Genomes ( FlyBase ), core data resource for C.

elegans and other nematodes ( WormBase ), Xenopus Biology & Genomics Resource ( Xenbase ) , Zebrafish Model Organism Database ( ZFIN ), Mouse Gene Expression Database [ ( GDX ], ), Chick Gene Expression Database ( GEISHA /Aviport ), Rat Genome Database ( RGD ), the Collaborative Cross mouse strains, and the NIH Center for Regenerative Medicine ( NIH CRM ) databases.

Assays should allow for direct functional measures of normal and altered biological processes and/or anatomic structure. Assays should typically be conducted in vivo (in a relevant animal-model) and/or in vitro (in cell- or tissue-based models). Functional assays conducted in vitro or cell-free biochemical assays should be verified in vivo in an animal model.

Providing multiple lines of convergent evidence supporting functionality using a combination of in silico, in vitro , and in vivo models is encouraged. Applicants are encouraged to provide a timeline for achieving the major goals stated in the application and describe metrics for evaluating achievement of the goals and what action will be taken, and when, if a goal is not met or significantly delayed.

Non-responsive applications: Projects with the following properties will be considered non-responsive, and will not be reviewed: Projects proposing large scale sequencing of birth defects cohorts will be considered non-responsive to this FOA. Investigations should be focused on existing sequence data available through publicly available databases or identified via individual/group efforts such as ClinGen Expert Curation Panels.

Projects that do not test the function of human genomic variants. Projects that do not test genomic variants associated with congenital anomalies. Projects proposing only cell-free biochemical assays to validate genomic variants.

Assays conducted exclusively in in vitro systems.

Assays not validated in an animal model Research Interests of Participating NIH Institutes and Office Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ): For this NOFO, NICHD encourages applications proposing to screen, functionally validate, and characterize genetic variants associated with children born with the following conditions: Structural congenital anomalies (SCAs) Intellectual developmental disabilities (IDDs) Inborn errors of metabolism (IEMs) Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from NICHD are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII.

Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with NICHD's program priorities.

National Institute of Dental and Craniofacial Research ( NIDCR ): NIDCR encourages applications proposing studies that will generate insights into the developmental etiology of rare or common human congenital anomalies, affecting dental, oral, and craniofacial structures. Data available on the NIDCR-supported FaceBase Hub ( www. facebase.

org ) may be utilized to support variant prioritization. Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from NIDCR are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII.

Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with NIDCR's program priorities.

Office of Research Infrastructure Programs ( ORIP ): ORIP encourages applications that are relevant to ORIP's mission to support research infrastructure and research-related resource programs, such as development of new technologies for generation and distribution of animal models of human diseases.

The technologies to create animal models of human genetic variants associated with human congenital anomalies and related materials must have broad application to multiple NIH Institutes or Centers (ICs) to align with the ORIP’s trans-NIH mission.

The following are examples of potential research topics: Improving methods to rapidly and efficiently generate non-mosaic germline and somatic human genomic variants to model disease-specific genomic alterations (coding and not coding), including robust phenotyping to assess if species genetic changes recapitulate a human phenotype. Tools for a conditional and tissue specific genome modifications are of special interest.

Approaches for generation of complex genetic mutations or larger structural variants (SV) (deletions, duplications, inversions). Combining model organism genomic modifications with phenotyping assays including detailed molecular analysis (omics profiling) which should be sufficiently integrative to assist high throughput interpretation of disease processes shared in model organisms and human patients.

Assess the effect of species genetic background of specific animal model species used to model a variant on the presentation and penetrance of a given phenotype. Program Directors/Principal Investigators (PD/PIs) planning to submit applications to this NOFO to be considered for funding from ORIP are strongly encouraged to contact the scientific contact prior to submission (see Scientific/Research Contacts in Section VII.

Agency Contacts) to be advised on appropriateness of the intended research plans for this program, competitiveness of a potential application, and alignment with ORIP's program priorities. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. 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 The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are limited to $499,999 direct costs per year and need to reflect the actual needs of the proposed projects. 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 NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) 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. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

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.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; 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 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 their organization to develop an application for 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 How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

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, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

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 NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: 1) Describe the human congenital anomaly under investigation and the dataset from which variants will be selected, as well as the public database through which these data are accessible, where applicable.

2) Describe how in-silico analysis, in vivo analysis and/or cell-based assays will be used to identify and prioritize variants. Include an explanation of how sex differences will be accounted for. 3) Describe the assay(s) and/or model system(s) that will be used to validate the selected variants.

Explain why this approach is expected to recapitulate or otherwise inform the phenotype under study. Using a combination of in silico, in vitro , and in vivo models is encouraged. If conducting in vitro or cell-free biochemical assays, explain how this will be verified in an in vivo animal model.

4) Explain why the data generated from this project will be of high value to the human congenital anomalies research community and/or potentially inform the development of strategies for the molecular diagnosis, treatment, or prevention of human congenital anomalies. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 2.

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. 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 Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications . 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 How to Apply-Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. 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 Section 7.

9. 1 Selected Items of Cost. 7.

Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply 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. All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form .

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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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 components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud,