Microphysiological Systems (MPS) for Modeling Diabetes (UG3/UH3 Clinical Trial Not Allowed) | RFA DK 17 035

Frequently Asked Questions (FAQs): NIH/NIDDK RFA-DK-17-035 (MPS-MOD)

1) What is this funding opportunity trying to support?

This NIH/NIDDK funding opportunity (RFA-DK-17-035) supports the creation of a research consortium to build and validate advanced human "tissue chip" models, formally described as Microphysiological Systems for Modeling Diabetes (MPS-MOD). The goal is to develop lab-based, human-relevant platforms that reproduce key aspects of normal metabolic physiology and then reliably show how that physiology shifts toward diabetes and metabolic disease.

2) What are Microphysiological Systems for Modeling Diabetes (MPS-MOD)?

MPS-MOD are engineered human tissue chip platforms designed to capture meaningful, multi-dimensional functions of metabolic tissues. They are expected to go beyond basic cell survival and instead provide measurable functional outputs relevant to diabetes biology, including responses to perturbations and therapeutics.

3) What is the programmatic rationale behind building these tissue chips?

The program is positioned as an enabling step toward faster and more predictive diabetes therapeutic discovery. The intent is to provide model systems that are more faithful to human biology than many traditional cell culture or animal models, improving the ability to study disease mechanisms and evaluate potential therapies in human-relevant systems.

4) Which tissues are specifically prioritized for modeling?

The scientific focus is on microphysiological systems representing major metabolic tissues involved in diabetes and metabolic dysfunction: pancreatic islets, liver, skeletal muscle, and white adipose tissue (WAT).

5) Is simply keeping cells alive in a chip sufficient for this program?

No. Applicants are expected to engineer systems that capture multi-dimensional tissue function and produce measurable responses that matter for diabetes research. The platforms should be built to quantify functional and pathophysiological changes relevant to metabolic disease.

6) What kinds of disease-relevant changes are applicants expected to measure?

The solicitation emphasizes quantifying pathophysiological changes linked to metabolic disease, including immune-metabolic interactions. Because inflammation and immune-metabolic crosstalk can be central drivers of metabolic dysfunction, experimental designs are expected to include approaches to evaluate immune cell interactions with metabolic tissues where appropriate.

7) How important is validation in this opportunity?

Validation is a central pillar. The usefulness and credibility of each MPS-MOD platform will be judged partly by whether established diabetes therapeutic agents and known biomarkers produce expected, biologically meaningful changes in the system.

8) What does validation look like in practice based on the description provided?

The models should be able to be challenged with well-characterized drugs or perturbations and then generate readouts that reflect known diabetes biology. The expectation is that the platform responses align with established therapeutic effects and biomarker behavior, supporting confidence that the model is predictive and biologically grounded.

9) Does the announcement emphasize rigor and reproducibility?

Yes. The solicitation stresses the use of best practices and rigorous study design. Reproducibility, appropriate controls, careful benchmarking, and credible performance evidence are presented as core measures of success rather than optional features.

10) What role do induced pluripotent stem cells (iPSCs) play in this program?

iPSCs are a major pillar of the opportunity. NIDDK highlights the importance of high-quality, well-characterized iPSC resources and standardized differentiation protocols, including the use of isogenic lines and patient-derived lines, to make disease-specific tissue chip models reliable and scalable.

11) Are standardized differentiation protocols explicitly encouraged?

Yes. The description notes that standardized differentiation protocols are critical so that disease-specific models become reliable tools rather than one-off demonstrations.

12) What is the longer-term vision for iPSC-based tissue chips described here?

The long-term vision is that iPSC-based tissue chips could become routine assets for drug development workflows, including screening, repurposing, and toxicity testing, using scalable human systems with interpretable endpoints.

13) What is meant by "clinical trials in a dish" in this context?

The opportunity points toward future use of collections of iPSCs reflecting the genetic and phenotypic diversity of type 2 diabetes (T2D). These could be used to identify biomarkers of drug response and support more personalized treatment strategies, effectively enabling a lab-based analogue of studying diverse patient responses.

14) Does this program require or encourage a consortium approach?

Yes. The opportunity supports creation of a research consortium, indicating an intent to fund coordinated platform development and validation efforts rather than isolated, standalone projects.

15) What kinds of expertise are expected on applicant teams?

Competitive applications are expected to be multidisciplinary, bringing together expertise in stem cell biology, bioengineering, computational biology, pharmacology, and domain-specific biology relevant to liver, islet, adipose tissue, metabolism, and diabetes.

16) What does the opportunity imply about the end-to-end workflow teams should be able to handle?

The intent is to assemble integrated teams that can manage the full pipeline: selecting and characterizing iPSC lines; differentiating cells into relevant tissue types; building microengineered platforms; integrating immune components where appropriate; defining robust functional readouts; and applying analytic and computational methods to interpret complex, potentially multi-tissue data.

17) What funding mechanism is used?

This opportunity uses a cooperative agreement mechanism under a UG3/UH3 structure.

18) What does the UG3/UH3 structure imply for the project?

It implies an initial milestone-driven development phase (UG3) followed by a second phase (UH3) that proceeds only if agreed-upon performance and validation benchmarks are met.

19) What does "cooperative agreement" imply about NIH involvement?

It indicates NIH staff will have an active stewardship role consistent with cooperative agreements, rather than a purely hands-off role.

20) Are clinical trials allowed under this opportunity?

No. Clinical trials are not allowed under this funding opportunity.

21) Which NIH institute is associated with this program?

The program is housed within the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the National Institutes of Health (NIH).

22) What are the listed CFDA numbers associated with this opportunity?

The provided record lists CFDA numbers 93.350 and 93.847.

23) Who is eligible to apply (in general terms)?

Eligibility is described as broad across U.S.-based organizations, including many government entities, public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses. The description also includes eligible tribal entities and housing authorities.

24) Are community-focused and mission-relevant institution types called out as eligible?

Yes. The announcement specifically calls out various mission-relevant institution types and community-focused organizations as eligible, including HBCUs, Hispanic-serving institutions, AANAPISIs, TCCUs, and faith-based or community-based organizations.

25) Are non-U.S. (foreign) institutions eligible to apply?

No. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply.

26) Can a U.S. organization include non-U.S. components?

Non-domestic components of U.S. organizations are not eligible. However, foreign components (as defined by the NIH Grants Policy Statement) are allowed, meaning discrete project elements may be performed abroad under specific conditions while the applicant organization remains U.S.-based.

27) What are the key dates provided in the record?

The provided record includes a creation date of December 11, 2017, and an original closing date of March 20, 2018.

28) Does the provided excerpt specify an award ceiling or the expected number of awards?

No. The award ceiling and expected number of awards are not specified in the provided excerpt.

29) What does the excerpt imply about the scale or intent of funding?

While specific funding amounts are not listed, the scope and consortium framing suggest an intent to fund coordinated, high-impact platform development and validation rather than isolated exploratory efforts.

30) What types of outputs or deliverables are implicitly expected from funded projects?

Based on the description, the expected outputs are validated, credible microphysiological tissue chip platforms for key metabolic tissues, supported by rigorous benchmarking data showing that known diabetes therapeutics and biomarkers produce expected, biologically meaningful responses, with strong study design and reproducibility practices.