Part 1. Overview Information

Key Dates

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.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

There are important clinical implications to basic research on early development. Abnormalities in embryonic development that result in birth defects are likely to involve the disruption of many cellular signaling cascades that would usually direct normal embryonic development. For example, developmental pathologies such as CAKUT (congenital anomalies of kidney and urinary tract) are thought to involve genetic regulatory pathways. In addition, embryonic developmental signaling networks have been shown to be reutilized later in the adult and may become dysfunctional and contribute to during disease progression. Furthermore, embryonic developmental factors are emerging as important participants in adult regenerative and repair processes. Thus, a comprehensive understanding of how organs develop in the embryo is necessary to effectively interrogate maladaptive processes and understand regeneration. Successful development of cell-based therapies to replace or repair damaged tissue will require knowledge of the catalog of cell types that contribute to the formation of an organ; the genes that mark these cells, as well as those that are required for their function; the regulatory factors that induce or maintain the various cell types; and the developmental and anatomic relationships of each cell type to its neighbors.

As a result, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsored the GenitoUrinary (GU) Development Molecular Anatomy Project (GUDMAP) in 2002, and in 2011 NIDDK renewed GUDMAP to continue efforts to (1) develop a low resolution gene atlas of all genes expressed within the developing mouse kidney and lower urinary tract, (2) perform high resolution anatomic gene expression studies using available or newly generated molecular tools, and (3) produce an integrated, continuously updated database that provides the entire research community with access to the data as it is generated. In 2016, NIDDK continued its support of GUDMAP and added studies that include human tissue.

The GUDMAP consortium has generated a mouse molecular atlas of the kidney and lower urinary tract in the developing embryo and a human molecular atlas of the developing kidney and prostate. The GUDMAP website allows access to the atlas. To date the database contains >460 microarray CEL files and >13,027 whole-mount or section imaging samples (11,454 in-situ hybridization images, 1,176 immunohistochemistry images, 380 histology slide images, and 17 nanoCT scans) representing 22,971 genes. Transcriptional profile datasets include 375 bulk RNA seq datasets collected from various renal sub-compartments captured by laser and from the use of translating ribosome affinity purification (TRAP). 218 single cell/single nuclei RNA-Seq datasets with visualization images covering 19,515 genes are included in the database. All data are annotated in detail against a standard anatomical ontology developed by the GUDMAP consortium that is updated as data reveals new genetic sub-compartments. In addition, the database houses data sheets on 150 characterized transgenic lines and 80 antibodies and supports 81 protocols.

Molecular markers have now been identified for physiologically or anatomically defined cell types within the mouse kidney and for developmental functional domains. This fundamental description of the kidney, for example, provides a significant resource to support research in kidney repair and regeneration, including stem cell research, where the design of novel therapies relies on knowledge of the cell types within an organ to determine whether putative therapies are effective at regenerating or restoring their functionality. The amount of data now present in the database has reached the stage where analyses are increasingly informative and are readily used by the research community.

Despite these advances, there remain significant knowledge gaps within the atlas for the organs of the lower urinary tract. There is a paucity of cell-specific markers for key lineages of the lower urinary tract organs and structures, and an absence of knowledge regarding the three-dimensional cellular structure and the morphogenetic events that occur during organogenesis. In addition, there is an incomplete understanding of the normal innervation and vasculature and of the lymphatics of the kidney and lower urinary tract.

Research Objectives

The new GUDMAP consortium will build upon the existing database and website infrastructure. It will retain the long-term objectives of GUDMAP to establish a comprehensive understanding of urinary tract development through the generation of data to visualize the developing urinary tract, to identify new functional and anatomical domains, and cell types, and to determine cell-fate relationships, and through the development of research tools (e.g., characterization of antibodies). It is expected that the efforts of the GUDMAP consortium will work synergistically with the NIDDK Kidney Precision Medicine Project and NIH-sponsored atlas efforts (e.g., The Human BioMolecular Atlas Program).

GUDMAP Consortium

This FOA invites applications for Atlas Projects that will work together as a consortium with the combined GUDMAP/RBK Data Hub (RFA-DK-20-014). The Data Hub will oversee the incorporation of data generated by the GUDMAP Atlas Projects and RBK Research Projects into a single data repository. The Data Hub will serve as the public face of the consortium and carry out administrative duties.

GUDMAP Atlas Projects

GUDMAP Atlas Projects should fill gaps in the atlas and take advantage of the GUDMAP framework and be designed to allow mouse/human comparisons through the establishment of common anchor/marker genes and tissue-specific developmental landmarks. GUDMAP Atlas Projects are encouraged to encompass developmental timelines that span embryogenesis to post-natal or early adolescence and include time points that reflect tissues/cellular changes in response to normal physiology, i.e., transition from liquid to solid food diet, development of bladder control etc. It is expected that the human atlas will inform the development of animal models of human developmental defects and diseases, although the generation of new mouse disease models will not be part of this FOA.

GUDMAP Atlas Projects are limited to human or mouse studies and are dictated by the need to fill knowledge gaps and should not overlap with other atlas efforts, e.g., HuBMAP. Studies are limited to the following tissues:

• Human tissues
  • Normal development of the vascular or lymphatic system or innervation of the kidney and lower urinary tract.
  • Normal development of the lower urinary tract, including the external male genitalia.
• Mouse tissues
  • Normal development of the lower urinary tract, including the external male genitalia
  • Normal development of the vascular or lymphatic system or innervation of the kidney and lower urinary tract.
  • development of the lower urinary tract, including the external male genitalia of mouse pre-clinical models of urinary developmental diseases or defects (e.g., congenital anomalies of the lower urinary tract) to validate (or invalidate) the model.

Types of tissue interrogation may include, but are not limited to:

• Large-scale spatial analyses of gene/protein expression of developing tissues utilizing whole-mount in situ hybridization, or other in situ approaches (multiplexing high-throughput RNA-FISH) or using libraries of antibodies (i.e., Codex). It is expected that this type of approach will take advantage of the GUDMAP atlas to provide the framework to develop distinct gene expression signatures in cell types of relevant tissues at a single time during development, expanding to a second time point if possible.
• Broad chromatin and transcriptional profiling of developing tissue to identify and enrich regionally groups of cells to define compartments and sub-compartments and to establish key genetic markers, i.e., anchor genes.
• Low resolution analyses of gene expression through developmental time (embryogenesis to post-natal or early adolescence), using high-throughput strategies, but focusing on a restricted set of genes. This approach may be suited to study the expression of a given class of gene products, e.g., transmembrane proteins.
• High resolution, three-dimensional analyses of a set of genes or gene products using, for example, tagged gene constructs, antibodies, or section in situ hybridization. Various types of imaging may be useful, including confocal microscopy, optical tomography, micro-MRI, Nano-computed tomography etc. The goal is to produce three dimensional representations of gene expression patterns and relate them to functional, anatomical, or molecular hallmarks.
• Analysis of gene expression programs in critical cell types using state of the art technology to establish a set of novel cell type specific molecular markers. Labeled cells/tissues may be generated via knock-ins, transgenic, or other methods.
• Utilize state-of-the-art computational/bioinformatic approaches to analyze data through the integration of various omic modalities (eg. scRNA-seq, ATAC-seq, Slide-seq, etc.). Analysis should also incorporate existing molecular data sets in GUDMAP/RBK as well as data sets in other repositories (eg. HuBMAP, HCA, KPMP) to uncover novel molecular pathways and cell-to-cell communication networks
• Tool development to advance a comprehensive understanding of lower urinary tract development.

Hypothesis generation is a goal of this FOA. Experiments to test these hypotheses are more suitable for investigator initiated R01 applications and are beyond the scope of this FOA. Furthermore, applications that plan to test newly generated hypotheses will be considered non-responsive and will be withdrawn from review . Likewise, projects designed to test hypotheses based on previously generated data will also be considered non-responsive and will be withdrawn from review .

GUDMAP Structure and Organization

The GUDMAP consortium is designed to serve as a resource to the research community. Therefore, the GUDMAP Atlas Projects (RFA-DK-20-013) and GUDMAP/RBK Data Hub (RFA-DK-20-014) must be well integrated, coordinated, and members must be willing to share materials freely within the consortium and the research community. All participants are required to agree to participate as active members of the GUDMAP consortium (see Cooperative Agreement Terms and Conditions of Award) and as appropriate to work together to (a) improve the quality of the existing data within the GUDMAP/RBK data repository and thereby enhance the utility of the GUDMAP data for the research community, (b) extend the data content of the GUDMAP specific data within the data repository by way of the presentation of bioinformatics results from existing analyses, and (c) improve the accessibility and utility of GUDMAP generated data to end users. GUDMAP Atlas Project participants are required to distribute all GUDMAP generated research tools (e.g., probe sets, antibody libraries, transgenic or knock-in mouse strains, cell lines, technologies, protocols, bioinformatic algorithms, etc.) and data to the wider community upon validation and prior to publication. It is expected that the successful applicants will actively participate in the development and monitoring of the ontology relevant to their project to ensure the integrity of ontology for all the tissues of the kidney and lower urinary tract, and to ensure the utility of the data repository for all researchers. As a member of the GUDMAP Consortium it is expected that individuals will closely interact and share resources with the (Re)Building a Kidney consortium and the NIDDK Kidney Precision Medicine Project.

During the funding period, technologies will improve, and the rate of progress and focus of work supported by the cooperative agreement might change. It is expected that the Program Directors/Principal Investigators, in consultation with the GUDMAP/RBK Data Hub, NIDDK program staff, and the Consortium Management Board, will make any necessary adjustments to accommodate the changing research environment, in order to remain focused on overall consortium goals and to maintain excellent coordination with the other projects and to incorporate new technological advances.

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

Section II. Award Information

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

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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• 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.

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.
  • 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.
• 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.

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

Number of Applications

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

Letter of Intent

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:

John F. Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email:[email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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.

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

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

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

Willingness to Participate: Please entitle this attachment "Willingness to Participate" and include a statement indicating a willingness to:

• Work with NIDDK and the Consortium to attend the initial meeting in person and the annual meetings during the course of the grant award;
• Cooperatively interact with NIDDK and Consortium in support of the projects and activities;
• Actively seek input from NIDDK and the Consortiums regarding resource or expertise needs that may arise during the performance of the project; and
• Participate in monthly conference calls.

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

R&R or Modular Budget

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

There will be annual meetings of the Consortium. The initial meeting will be held in Bethesda and subsequent meeting may be held at an GUDMAP Atlas Project or GUDMAP/RBK Data Hub site. Applicants should request a budget for costs of the PD/PI and other essential members of the Atlas Project to attend these meetings.

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Investigators who have generated GUDMAP data as part of a subcontract may submit these data in the Preliminary Studies for New Applications section within the Research Strategy.

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, should address a Data Sharing Plan and a statement that all data, tools and materials will be rapidly shared, prior to publication, with the general research community.
• Applicants are expected to include a plan addressing if, or how, they will exercise their intellectual property rights while making available to the broader scientific community patentable research resources as appropriate and consistent with achieving the goals of this program. These plans must be fully supported by the applicant's institution.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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 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.

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.

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

Foreign Institutions

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

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.

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.

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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

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.

For this announcement, note the following:

In addition to standard review criteria, all applications will be judged on the documented ability of the investigators to conduct the work proposed.

As such this new GUDMAP consortium will build upon the existing database and website infrastructure, and will retain the long-term objective of the GUDMAP consortium to establish a comprehensive understanding of kidney and lower urinary tract development and maturation to inform the study of tissue maturation and aging, organ dysgenesis and disease, and ultimately organ repair and regeneration. Thus, it is expected that proposed human or mouse studies will fill knowledge gaps and should not overlap with other atlas efforts and that generated human data will inform the development of animal models of human developmental defects and diseases

It is expected that the proposed studies will be very effective at generating hypotheses. Hypothesis generation is a goal of the initiative, not hypothesis testing.

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).

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.

Significance

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?

Specific to this FOA: Where applicable: Will the generated human data provide distinct gene expression signatures in cell types of relevant organs and help inform thedevelopment of mouse models of human developmental defects or diseases? Do the genes chosen for high resolution analysis mark distinct cell populations? Can the expression of these genes be correlated to anatomic landmarks? Are the gene sets chosen for high-throughput studies well justified? Will the tools to be generated be useful for the community?

Investigator(s)

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?

Specific to this FOA: Is there evidence that the investigators will collaborate extensively and share information fully within the consortium? Is there evidence that the investigators will facilitate and coordinate efforts with the consolidated GUDMAP/RBK Data Hub? Do the investigators have appropriate experience and training to participate in the development and monitoring of the ontology relevant to their project?

Innovation

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?

Approach

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?

Specific to this FOA: Where applicable: Does the Human GUDMAP Atlas Project take advantage of the GUDMAP atlas and facilitate the generation of anchor genes and developmental landmarks that can be used for comparison with the developing mouse organ? Is there an overall strategy to develop the ontology and annotation for mouse Atlas Projects? Is the developmental timeline well thought out and are the time points based on physiological changes? Are the mouse pre-clinical models chosen for interrogation well thought out and do they take advantage of the GUDMAP atlas?

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?

Environment

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?

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

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.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs using 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.

Select Agent Research

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).

Resource Sharing Plans

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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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(s) convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 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 will receive a written critique.

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.

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 National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). 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.
• Compliance with resource sharing policies and the evidence for willingness to work cooperatively.
• Likelihood for substantial contribution by the applicants to a successful collaborative effort.

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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. 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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides 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/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, 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.

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the scientific activities, including defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• Collaborating with other investigators in the program for protocol development, sample, reagents and data sharing as appropriate, data quality control, and data organization.
• Accountability towards the applicant organization officials and to the NIDDK for the performance and proper conduct of the research supported by the project in accordance with the terms and conditions of the award.
• Serving as a voting member of the Steering Committee (SC) and will attend the Planning Meeting and a SC meeting in the first year, and annually in subsequent years, and will participant in monthly teleconference calls.
• Accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the SC and subcommittees and be responsible for close coordination and cooperation with the GUDMAP/RBK Data Hub and with NIH staff.
• Adhering to PHS policy for the distribution of unique research resources produced with PHS funding as described under Special Requirements.
• Establishing written milestones for the project, in negotiation with NIDDK Project Staff prior to funding, if requested.
• Release all study design materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NIDDK, for the conduct of research at no charge other than the costs of reproduction and distribution, consistent with achieving the goals of this program initiative.
• 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.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. However, the dominant role and prime responsibility for the project as a whole resides with the awardees, although specific tasks and activities in carrying out the studies will be shared by awardees and the NIDDK.
• NIDDK will designate a Project Officer and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement.
• NIDDK will form a Consortium Management Board (CMB), comprised of the NIDDK Project Scientist and other NIH extramural staff with relevant scientific expertise or who manage research grant programs that relate scientifically to the goals of the GUDMAP Atlas Projects, and outside advisors selected by the NIDDK. The CMB will meet annually with the GUDMAP SC to review and assess the GUDMAP consortium and to advise NIDDK of scientific developments and opportunities that may enhance the achievement of the GUDMAP goals.
• The NIDDK Project Scientist will attend and participate as a voting member in all meetings of the SC and provide liaison between the SC and the CMB.
• The NIDDK Project Scientist will help the SC develop and draft operating policies.
• The NIDDK Project Officer will review the scientific progress of the individual GUDMAP Atlas Projects, for compliance with operating policies developed by the SC, and may recommend to the NIDDK to withhold support, suspend, or terminate an award for lack of scientific progress or failure to adhere to policies established by the SC.
• An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Officer may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

• The NIH Project Scientist, PIs from the project funded through this FOA and RFA-DK-20-14 will be responsible for forming a SC as defined below. An arbitration system, as detailed below, will be available to resolve disagreements among members of the SC. The SC will be the main governing board of the GUDMAP consortium. It will develop collaborative protocols, identify technological impediments to success and strategies to overcome them, develop shared software tools for disseminating information about the projects, and identify opportunities for sharing techniques and tools that might be developed in future GUDMAP Atlas Projects.
• The SC will be composed of the PIs from the project funded through this FOA, RFA-DK-20-14 and the NIDDK Project Scientist. The representatives and the PIs will each have one vote. The NIDDK Project Scientist for this project will have one vote. The SC will select a chairperson who will be someone other than an NIH staff member.
• The SC may, as it deems necessary, invite additional, non-voting scientific advisors to meetings at which research priorities and opportunities are discussed. The NIH reserves the right to augment the scientific or consumer expertise of the SC when necessary.
• There will be an annual SC meeting. The first meeting will be a Planning Meeting to be held in the Washington, DC area. At the Planning Meeting, the SC will be formed, and a chairperson selected from among the members. At the Planning Meeting, the SC may: (a) draft a charter to detail policies and procedures, a process for monitoring compliance with the policies and procedures, and a process for recommending that the NIH Project Administrators act on evidence of non-compliance of any Consortium component with SC policies; (b) agree upon the terms of the charter; and (c) devise a plan for working with the GUDMAP/RBK Data Hub to provide ongoing input into database and website design.
• At the second and subsequent meetings, the SC will refine the GUDMAP scientific objectives and implementation as necessary, consistent with data produced by former and possible future GUDMAP Atlas Projects and from other laboratories.
• The SC may plan workshops, to which non-GUDMAP participants will also be invited, to inform the research community of the progress made toward development of the atlas, and to inform the research community of any technological advances related to the implementation of the GUDMAP/RBK Data Hub. The NIDDK Project Scientist, the CMB, and other NIH staff as appropriate will provide the SC with advice on participants for the workshops and symposia.
• The SC may establish subcommittees as it deems appropriate.
• Awardee members of the SC will be required to accept and implement policies approved by the SC.
• The CMB will meet annually with the GUDMAP SC to review and assess the progress of the GUDMAP consortium and to advise NIDDK of scientific developments and opportunities that may enhance the achievement of the GUDMAP goals.

Dispute Resolution
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 Dispute Resolution. A Dispute Resolution Panel 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 dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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 agreements are 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.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission 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: [email protected] (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: [email protected]

Eric W. Brunskill, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: (301) 215-1698
Email: [email protected]

Ryan Morris, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-1296
Email: [email protected]

Charlette Kenley
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8847
Email:[email protected]

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.

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.