Part 1. Overview Information

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

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title
Human Islet Research Network - Consortium on Human Islet Biomimetics (HIRN-CHIB) (UG3/UH3 Clinical Trial Not Allowed)
Activity Code
UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement
Announcement Type
New
Related Notices
None
Funding Opportunity Announcement (FOA) Number
RFA-DK-18-011
Companion Funding Opportunity
None
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.847
Funding Opportunity Purpose
This FOA invites new applications to participate in the Human Islet Research Network-Consortium on Human Islet Biomimetics (HIRN-CHIB). NIDDK will support the development of a microphysiological system (MPS) that allows the study of interactions between primary human islets or assembled islet spheroids (organoids made up of human beta/alpha/delta/other cells) and immune cells within a 3D microenvironment to mimic aspects of the autoimmune process and its regulation. The ultimate goal will be to create an in vitro human disease model(s) that could recapitulate some aspects of the complex pathophysiology of Type 1 diabetes (T1D), by using T1D patient-derived islets (created using induced pluripotent stem cells (iPSCs) combined with autologous immune components.  CHIB is already part of HIRN, whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. 

Key Dates

Posted Date
August 10, 2018
Open Date (Earliest Submission Date)
November 11, 2018
Letter of Intent Due Date(s)
November 11, 2018
Application Due Date(s)
December 11, 2018, 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.

AIDS Application Due Date(s)
Not applicable
Scientific Merit Review
February/March 2019
Advisory Council Review
May 2019
Earliest Start Date
July 2019
Expiration Date
December 12, 2018
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

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

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

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This FOA invites new applications to participate in the Human Islet Research Network-Consortium on Human Islet Biomimetics (HIRN-CHIB). NIDDK will support the development of a microphysiological system (MPS) that allows the study of interactions between primary human islets or assembled islet spheroids (organoids made up of human beta/alpha/delta/other cells) and immune cells within a 3D microenvironment to mimic aspects of the autoimmune process and its regulation. The ultimate goal will be to create an in vitro human disease model(s) that could recapitulate some aspects of the complex pathophysiology of Type 1 diabetes (T1D), by using T1D patient-derived islets [created using induced pluripotent stem cells (iPSCs)] combined with autologous immune components.  CHIB is already part of HIRN, whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans.

The need for high quality, well-characterized isogenic/patient-derived iPSC lines and standardized differentiation procedures for achieving maturation of beta cells and other pancreatic islet subtypes is a critical step for HIRN-CHIB. Expansion of islet chip capabilities such as multiplexed hormone sensing, instrumentation and systems engineering for robust control of fluidic and biochemical cellular microenvironments, the integration of bioanalytical systems, and incorporation of novel microfluidic systems that permit the controlled introduction of both stimuli and cells, coupled with the assessment of their impact on islet stress and function will be needed. CHIB will lay the groundwork for establishing reproducible and translatable MPS platforms that are capable of modeling key aspects of T1D pathophysiology. An essential feature of HIRN-CHIB will be a multidisciplinary approach that brings together basic science experts and physician scientists in stem cell biology, bioengineering, immunology, islet biology and T1D.

Funds from the NIDDK will be made available through the UG3/UH3 cooperative agreement award mechanism.  The UG3 phase should include sensitive on-chip assays that measure normal islet function.  The UG3/UH3 phase should use primary human tissues to help characterize both the maturity and adult function of iPSC-derived tissues, and by the end of the UH3 phase, assembly of an iPSC-based MPS model of T1D should be well-underway. 

Background

CHIB has focused on deriving engineered platforms that support the survival, maintenance and function of cadaveric human islets for periods of time up to 4 weeks. Interdisciplinary teams have combined technological advances and knowledge in islet biology, stem cell biology, and microengineering to accelerate progress in creating a human islet biomimetic or MPS. CHIB has generated a network of blood vessels around human islets in microdevices to deliver oxygen, nutrients and promote islet health, developed extracellular matrices that support islet function and survival, and continues to integrate robust, reproducible, and sensitive assays to monitor islet function (such as dynamic insulin secretion). These platforms will enable future investigations focused on how human islets and immune components interact, and provide insight as to how beta cells are lost in T1D.  The Consortium on Modeling Autoimmune Interactions (CMAI), also part of HIRN, has been working on the development of "in vivo" humanized models of T1D, thus, the establishment of the in vitro platforms proposed here may support and complement research that is being advanced.

Research Objectives and Scope

UG3 Phase Objectives (up to 2 years)

The UG3 Phase should develop platform technology that allows the study of interactions between primary human islets/re-aggregated islet spheroids (organoids) and immune cells involved in the T1D inflammatory/autoimmune process, and its regulation within a 3D environment.

  • Devices should include the addition of flow for dynamic perifusion, with controlled inputs and outputs;
  • Incorporation of 3D technology to enable the controlled and targeted temporal and spatial introduction and removal of soluble factors or cellular components;
  • Incorporation of other supportive cells (endothelial cells, non-endocrine cells within the islet and/or tissues);
  • Introduction of reporter systems that will provide information in real-time to monitor beta cell function and health, as well as immune cell activation and effector/regulatory function;
  • Inclusion of primary human beta/alpha/other islet subtypes and immune populations involved in promoting islet inflammation and antigen-specific interactions;
  • Integration of sensitive and robust assays for insulin and glucagon secretion, as well as assays capable of measuring the health and function of other cells operating within the islet microenvironment;
  • Inclusion of a well-conceived plan to develop a human iPSC-based MPS consisting of human beta, alpha, and other islet subtypes, CD8/CD4/DC/other relevant immune components, and supportive cells such as endothelial cells, mesenchyme, and neural components, etc. This plan should include a strategy to achieve maturation and glucose-responsiveness of human iPSC-derived beta cells in a vascularized organoid platform.
     

UH3 phase Objectives (up to 3 years)

HIRN-CHIB's long-term goal is to develop personalized chips for studying T1D. To work towards this goal, an MPS to study islet/immune interactions using an autologous T1D patient based platform will require:

  • Generation of human iPSC derived islet organoids from individuals with T1D and pre-T1D, or iPSC-derived organoids from normal individuals that have been engineered to contain T1D-associated genetic risk variants;
  • Integration of human iPSC components into the platforms;
  • Cross-validation of T1D model endpoints with clinical measures in humans.
     

UG3/UH3 Milestones

All projects will be milestone-driven with clear go/no-go criteria that are quantifiable and milestones with a timeline, must be included in the application.  Prior to funding an application, the Program Official will contact the applicant to discuss the proposed UG3 and UH3 milestones and any changes supported by NIH staff or the NIH review panel.  The Program Official and the applicant will negotiate and agree on a final set of approved UG3 milestones which will be specified in the Notice of Award.  These milestones will be the basis for judging the successful completion of the work proposed in the UG3 stage and progress toward interim milestones in the UH3 stage.  Only UG3 projects that meet their milestones will have an opportunity to move to the UH3 phase.  UH3 milestones will be the basis for judging progress towards and completion of interim milestones in the UH3 phase. 

Studies of interest for both the UG3 and UH3 phases will examine key cellular and environmental factors controlling autoimmune killing of human cadaveric islets/iPSC-generated islet cell populations. These studies could include the following but are not limited to:

  • Identify potentially novel therapeutic targets to prevent beta cell killing or modulate Cytotoxic T Lymphocyte (CTL) effector mechanisms;
  • Examine the influence of HLA expression in beta cells on immune mediated responses in the MPS and develop strategies to monitor expression/production of autoimmune targets by islet cells, including altered antigens such as hybrid peptides;
  • Evaluate the impact of combining subsets of immune effector/regulatory cells in the MPS on islet/beta cell health and function, and quantify the magnitude of any resulting beta cell dysfunction or death;?
  • Directly compare the susceptibility of various bioengineered islets/cells to immune-mediated killing relative to primary human beta cells recovered from juvenile and adult donors;
  • Address mechanistic questions about immunomodulatory agents tested in clinical trials that have shown some clinical response (e.g. Abatacept, Teplizumab, ATG, Rituximab, etc.);
  • Study the role of stromal/support cells as promoting of beta cell preservation and function in the MPS environment;
  • Evaluate the impact of perifusion on soluble pathways of beta cell killing (cytokine storm);
  • Examine conditions that control islet/beta cell stress in the MPS and identify intrinsic factors that contribute to beta cell dysfunction/death in the context of an immune attack;
  • Define the role of human endothelial cells as modulators of islet cell health, and as contributors to the autoimmune process;
  • Characterize the impact of islet metabolic byproducts or glucose on immune cell function in the local MPS environment;
  • Study basic processes of immune cell attachment, integrin binding, chemokine gradient trafficking, degradation of extracellular matrix, etc. within and around beta cell/islets in the MPS platform to measure key features of human immune cell trafficking with the islet microenvironment;
  • Compare alloreactive versus autoreactive models of beta cell killing and their differential components;
  • Apply novel single cell technologies (RNA, chromatin, protein) to define cell heterogeneity and signatures of immune cells, islet cells and endothelial cells in the T1D islet niche within the MPS.

All methods, reagents, resources, biomaterials (including cell lines), protocols, data and models developed by HIRN-CHIB are expected to be made available to the research community.  Because individual UG3/UH3 projects will be coordinated through HIRN-CHIB, the timeline and processes for sharing within HIRN-CHIB, and with the community at-large will be established by the HIRN-CHIB NIDDK Project Scientist and the HIRN-CHIB PD(s)/PI(s).  All participants are expected to adhere to these policies as a term of the award, consistent with achieving the goals of the program.  Policy documents for HIRN-CHIB will be accessible in the HIRN website.

Meetings of HIRN-CHIB

Program Director(s)Principal Investigators(s) of HIRN-CHIB must participate in an initial in-person meeting soon after awards are made, in the annual HIRN Investigator's Scientific Retreat held in the spring, in CHIB teleconference meetings to be held at least tri-annually thereafter, and in the in-person HIRN-CHIB Scientific Fall Retreat, to be held annually. All participants must be obligated to abide by the policies adopted by the majority vote of the HIRN-CHIB Steering Committee. In the application, research project budget requests should include costs for the PD/PI and up to two other members of the individual project to attend the annual HIRN Investigator's Scientific Retreat and the annual in-person HIRN-CHIB meeting.

Additional Considerations

Cells: The use of transformed or immortalized cell lines is discouraged, except for preliminary, proof-of-concept studies. The use of primary cells and organ explants in initial studies, progressing to pluripotent stem cells, e.g. iPSCs is encouraged. The current NIH guidance on stem cell usage can be found at http://stemcells.nih.gov/policy/pages/2009guidelines.aspx

Collaborations: Collaborative interactions are a critical aspect of this FOA. The development of MPS(s) for modeling T1D will require extensive collaboration among tissue engineers, stem cell biologists, diabetes experts and clinicians. Additional funds may be made available at a later time to support collaborative studies with HIRN-Consortium on Beta Cell Death and Survival (CBDS), to validate or test new therapeutics/biomarkers for T1D, or with HIRN-CMAI, to facilitate complementary studies investigating islet cell/immune interactions in humanized animal models, and the cross-validation of T1D model endpoints with clinical measures in humans.

Applications that include the following types of studies will be considered non-responsive and will not be reviewed:

  • Development of 3D tissues for transplantation
  • Engineering of non-human tissue models
  • Development of simple organoid models that do not go significantly beyond those currently available and in use
  • Development of systems for which an informative animal model already exists
  • Clinical trials?
See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $3 million per year in FY 2019 to fund 2-3 awards.

Award Budget
Application budgets are limited to $750,000 direct costs per year for both the UG3 and UH3 phases.
Award Project Period
The maximum project period is 5 years, contingent on completion of milestones and research objectives, including a maximum of a 2 year UG3 phase and a maximum of a 3 year UH3 phase.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

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

Applicant organizations

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

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

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

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

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

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

3. Additional Information on Eligibility

 

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

 

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 Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: NIDDKLetterofIntent@mail.nih.gov

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

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

PDs/PIs are required to attend an initial kick-off meeting, the annual HIRN and CHIB meetings. Funds to support travel of the PD(s)/PI(s) and up to two additional team members to attend the kick-off meeting and bi-annual meetings should be included in the budget.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:


Specific Aims: Provide the overall goals for hypotheses for the entire project period and identify separate Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

Research Strategy: The applicant must:

  • Include plans for collaboration among the scientific fields relevant to this FOA, i.e. T1D disease expertise, clinical expertise, tissue chip developers, stem cell biologists

  • Provide separate sections that describe both the UG3 and UH3 phases

  • Provide a description of the hypothesis to be tested in the UH3 phase of the study

Go/No-Go Transition Milestones for transition from the UG3 Phase to the UH3 Phase:

The applicant must:

  • Include clearly identified Go/No-Go transition milestones for completion of the UG3 phase at the end of Year 2 and transition to the UH3 phase for 3 years  of additional funding.

  • A timeline (Gantt chart) including milestones is required for all studies.  Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years.

Milestones and the timeline for each stage must be provided for each UG3 and UH3 section and include the following:

  • Provide detailed quantitative criteria by which milestone achievement will be assessed.

  • Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.

  • Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

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.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or 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.

Delayed Onset Study

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

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Specific to this FOA, note the following:

The UG3/UH3 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research.  Although a UG3/UH3 grant application is not required to have extensive preliminary data, background material or preliminary information, some preliminary data to inform feasibility is required; these data should be included if available.  Appropriate justification for the proposed work can also be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge of understanding.  Reviewers will assign a single impact score for the entire application, which includes the UG3 and UH3 phase.

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

 

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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: In the project, is there a strong justification/rationale provided for transforming our understanding of normal human physiology of the pancreatic islet?  Is there a potential translational benefit derived for the development and use of the proposed MPS? Is the MPS able to recapitulate normal biological indicators of islet function? Does the proposed disease model recapitulate aspects of a clinically relevant model of Type 1 diabetes?  Does the application focus on critical gaps to address important questions or obstacles in Type 1 diabetes?  Will successful completion of the research aims promote an understanding of Type 1 diabetes pathogenesis and advance the future development of diagnostics and interventions?

 

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 the Multi-PI leadership plan, if applicable, well-described, including plans for dispute resolution? Have project leadership and other key personnel demonstrated a track record of directing and conducting research activities related to creating and validating an MPS, creating and characterizing an iPSC-derived tissue, and have the expertise to create and validate clinically relevant on-chip assays, and models of type 1 diabetes? Are the collaborations, in particular, from disease experts, well-documented, including provision of letters of support?  Does the application provide a feasible strategy for collaboration among the scientific fields relevant to this FOA, i.e. disease experts, clinicians, tissue chip developers, stem cell biologists?

 

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?

Specific to this FOA: Are the overall goals of the application conducive to generating significant multidisciplinary investigations that generate robust and reproducible protocols for generating iPSC derived tissues? Expanding islet chip capabilities such as multiplexed hormone sensing, instrumentation and systems engineering for robust control of fluidic and biochemical cellular microenvironments, the integration of bioanalytical systems, and incorporation of novel microfluidic systems that permit the controlled introduction of both stimuli and cells? Generating clinically relevant on-chip assays of function? Generating novel models for studies of type 1 diabetes that will advance basic and translational science and/or future therapy development?

Does the project utilize the current advances of cutting edge technologies? Are the tissue chip platforms, combined with iPSC derivatives being proposed suitable to capture features of normal islet function and is the MPS appropriate for modeling disease? 

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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: Has the applicant included an adequate description and justification of the MPS and disease model?  Are the technologies or experimental approaches state of the art or is there novel use of non-state of the art technology?  Will the expected results lead to advances in technologies used in understanding the normal function of the human pancreatic islet, as well as, the pathophysiology of Type 1 Diabetes?  Are the proposed approaches, tools, and technologies scientifically justified for the particular MPS and disease model?  Does the application identify major technical risks, and are the proposed efforts to mitigate or address the risks clearly defined and feasible? Is the proposed transition plan to the UH3 phase complete and in a logical sequence to the elements of the phased UG3/UH3?  Are the conceptual framework, testable hypothesis, design, bioengineered platform, microfluidics, biomechanics, iPSC source and differentiation protocols well-justified?

Milestones.  Are appropriate, clearly-defined quantitative milestones provided for the UG3 and UH3 phases of the overall project?  Are the UG3 and UH3 milestones feasible, well-developed and quantitative with regard to the specific aims within each phase?  Is the overall timeline feasible for the UG3 and UH3 phases?  Are the critical decision points (i.e. go/no go decision points) and timelines within the UG3 and UH3 phases appropriate?   Are adequate criteria provided in the UG3 phase to assess milestone completion in order to make a decision to advance studies to the UH3 phase?

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 children, justified in terms of the scientific goals and research strategy proposed?

 

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

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

 

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

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

 

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

 

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

 

Not applicable

 

Not applicable

 

Not applicable

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

 

Not applicable

 

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

 

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

 

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

 

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. 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. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

2. Administrative and National Policy Requirements

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 75, and other HHS PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement UG3/UH3, 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:

  • 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.
  • Assuming responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
  • Retaining custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH policies.
  • Maintaining the confidentiality of the information developed by the investigations, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators. This includes all staff of the PD(s)/PI(s)
  • Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the FOA.
  • Participating in a cooperative and interactive manner with NIH staff, one another and with the HIRN-CC in all aspects of CHIB. This includes all staff of the PD(s)/PI(s).
  • Sharing data, materials, models, methods, information and unique research resources that are generated by the projects in accordance with CHIB policies in order to facilitate progress.  When appropriate, and in accordance with NIH policies, PD(s)/PI(s) will be expected to collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities of other CHIB members.
  • Submitting a list of milestones and project deliverables to the HIRN CC prior to the initial HIRN meeting, and will update this list annually.
  • Establishing agreements amongst themselves that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications. 
  • Agreeing that industry collaborations should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures and any CHIB policies and procedures developed by the CHIB.
  • Operating in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
  • Upon completion or termination of the research project(s), making all study materials and procedures broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research.  The data sharing plan should include a plan to accomplish this at the end of the study.
  • When asked by NIH staff to scientifically review applications for special opportunity pool funds, agreeing to review applications, as deemed appropriate.

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

  • The NIDDK will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement.  The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
  • The NIH will invite experts with relevant scientific expertise to provide feedback to the NIH on CHIB activities.  The Expert Scientific Panel (ESP) will meet to review the progress of the research projects and to inform NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.
  • An NIDDK Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIDDK Program Official as follows:
    • The NIH Project Scientist will coordinate and facilitate the research projects, attend and participate in all meetings of the CHIB, and act as a liaison between the Awardee and the Expert Scientific Panel.
    • The NIH Project Scientist and Program Officer will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research in each of the individual research project, and review the project for compliance with operating policies developed by the CHIB.  Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of scientific progress or failure to adhere to policies established by the CHIB.  Review of progress may include regular communications between the Principal Investigator and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
  • The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or CHIB policy and procedure, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or (3) concerns related to human subject safety that prompt the need for premature termination.
  • The NIH Program Scientist and Program Officer will review applications for Special Opportunity Funds for responsiveness to program goals to insure that they are within the scope of CHIB research as described in the Funding Opportunity Announcement and NIH guidelines.
  • The NIH will enlist additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist in carrying out the goals and aims of the approved studies.  The NIH will have one vote for any key committees, regardless of the number of NIH consultants involved in the project.
  • The NIH Project Scientist will have substantial scientific programmatic involvement in research coordination and performance monitoring.  The dominant role and primary responsibility for these activities resides with the awardee, however, specific tasks and activities in carrying out the studies will be shared among the awardees and the NIH Project Scientist.
  • The NIH Project Scientist serves as a resource with respect to other ongoing NIH activities that may be relevant to CHIB studies to facilitate compatibility and avoid unnecessary duplication of effort.
  • The NIH Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.
  • The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.
  • The NIH Project Scientist may be a co-author on study publications.  In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas:  (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

Areas of Joint Responsibility include:

Through the Awardee(s) and NIH staff, CHIB will cooperatively develop and implement processes to submit information and data to the HIRN-AH, determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the Funding Opportunity Announcement.

There will be an initial face-to-face meeting of HIRN and a minimum of 2 CHIB meetings (teleconferences or face-to face meetings) annually. One of these bi-annual meetings could be combined with the annual HIRN Investigator Scientific Retreat.  Awardee(s), the CHIB Project Scientist, and the CHIB Program Official are expected to attend these meetings.  A team will be established through this program to enable multiple, but coordinated, approaches to advance this area of research.  If a single award is made, then CHIB will be governed by the PI and the NIH Project Scientist. 

Steering Committee

If multiple UG3/UH3s are funded, then CHIB Awardees agree to the governance of the study through a Steering Committee.

  • On an annual basis, and following input from the CHIB Steering Committee members, NIDDK staff will appoint a Steering Committee Chair who will be in charge of facilitating the CHIB Steering Committee meetings and teleconference.  In collaboration with the HIRN CC and the NIH Project Scientist, the Chairperson is responsible for coordinating the Steering Committee activities, for preparing meeting agendas and for chairing meetings.
  • The Steering Committee, including the Project Scientist, is responsible for establishing and implementing processes and criteria for recommending special projects for consideration for special opportunity funds by NIH staff.
  • The NIH Project Scientist may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees.
  • The Steering Committee will be composed of the Principal Investigators/Program Directors for each UG3/UH3, or by UG3/UH4 representatives (one per UG3/UH3 grant) chosen by the Principal Investigators/program Directors in the case of multi-PI grants, and the NIH Project Scientist.  Only the UG3/UH3 PI/PD or multi-PI UG3/UH3 representative and the NIH Project Scientist will be voting members of the Steering Committee and will attend all meetings of the Steering Committee.  Each full member will have one vote.  Other designated NIH program staff attending the steering committee meetings will be ex officio (non-voting) members.  The CHIB Steering Committee will meet at least twice a year.
  • All major scientific and policy decisions will be determined by voting policies as established by the Steering Committee at the initial meeting.  This committee will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools developed within each individual project.  Steering Committee activities and decisions will consider the advice of the External Experts.
  • The NIH Project Scientist will help the Steering Committee develop and draft operating policies.
  •  NIDDK staff, in concert with the Steering Committee, will have the option to redirect research activities being pursued within the UG3/UH3 grant(s) if it is considered beneficial to the overall program.
  • The awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees.
  • Awardees must serve on CHIB subcommittees as needed.  Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the HIRN Investigator Scientific Retreat.

HIRN Trans-Network Committee (HIRN-TNC)

The HIRN-TNC will consist of: the PI/PD of the HIRN CC, the PI/PD of the HIRN DCC, and the Steering Committee Chairs and Project Scientists of the HIRN scientific topic consortia (CHIB, CTAR, CMAI, CBDS, and HPAP); the TNC is not a governing body and does not cast votes.

  • The TNC will facilitate communication and foster collaboration across the different consortia. 
  • The TNC will be responsible for organizing the yearly HIRN Investigator Scientific Retreat.
  • The TNC will meet by teleconference at least bi-annually and will be organized by the HIRN CC.  Meetings will be used to discuss and prioritize, and review the progress of applications that will use "opportunity pool" funds.  Subcommittees of HIRN, as well as working groups for scientific planning may be established and require participation by the CHIB members through in-person, electronic, or teleconference meetings, as appropriate.  The HIRN CC is responsible for providing and maintaining a record of minutes of all EC meetings, which will be approved by the EC.

Expert Scientific Panel (ESP)

An independent panel of 2-5 External Experts will be appointed by the NIDDK and meet by teleconference with the CHIB Project Scientist and the CHIB Project Officer at least once a year.  The CHIB-ESP will be updated on progress and give feedback to the CHIB PI/PD, Steering Committee and NIH on adjustments and future directions for the CHIB research projects(s).  On an annual basis, and following input from the ESP members, NIDDK staff will appoint an ESP Chair who will be required to attend the annual HIRN Investigator Scientific Retreat, to participate in the CHIB Steering Committee meetings as ex-officio, and to serve as the CHIB-ESP representative to the larger HIRN-ESP that will also meet once a year.  The CHIB-ESP Chair will be tasked with relaying the CHIB Steering Committee recommendations for new Opportunity Funds Initiatives to the HIRN ESP.  All CHIB-ESP members will also be invited to listen as ex-officio to CHIB Steering Committee meetings.   Members of CHIB-ESP may be asked, on an ad hoc basis, in the peer review of applications for new research applications that request "opportunity pool" funds.  The HIRN-CC will support costs for teleconferences between the ESP and the CHIB Steering Committee, will arrange CHIB-ESP and HIRN-ESP teleconferences, maintain a record of minutes, and support costs for the CHIB-ESP chair to participate in the annual HIRN Investigator Scientific Retreat.

Intellectual Property

The successful development of disease models using microphysiological system platforms may require either substantial investment and support by private sector industries and/or may involve collaborations with other organizations such as academic, other government agencies, and/or non-profit research institutions not directly involved in CHIB.  NIH recognized that intellectual property rights are likely to play an important role in achieving the goals of this program.  To this end, all awardees shall understand and acknowledge the following:

  • The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
  • Before, during and subsequent to the award, the U.S. Government is no required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
  • The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Baye-Dole Act).

Dispute Resolution

Disagreements that may arise in scientific/technical matter or programmatic matters (within the scope of the award) between award recipients and the NIDDK may be brought to arbitration after first attempting to resolve the issue through the Steering Committee or its subcommittees, as appropriate.  An Arbitration Panel composed of three members will be convened.  It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee.  This special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

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

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative 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.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, 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 processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

Sheryl M. Sato, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8811
Email: smsato@mail.nih.gov

Peer Review Contact(s)

Elena Sanovich, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone:301-594-8886
Email: sanoviche@mail.nih.gov

Financial/Grants Management Contact(s)
Craig Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: bagdonc@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Authority and Regulations
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
This FOA is supported under the authority of P.L. 115-123, Bipartisan Budget Act of 2018; Section 50902. Extension for special diabetes programs. 


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