Opportunity Information: Apply for RFA DA 19 010
The National Institutes of Health (NIH) released this discretionary grant opportunity, RFA-DA-19-010, titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed)," to support early-stage, exploratory research on HIV-associated neurocognitive disorders (HAND) in the modern treatment era. The focus is on understanding the cellular and molecular mechanisms that drive neuropathophysiology in people living with HIV who are on long-term combination antiretroviral therapy (cART). Rather than relying solely on animal models or postmortem tissue, the FOA emphasizes the use of human stem cell-based systems, specifically patient-derived induced pluripotent stem cell (iPSC) lines that can be differentiated into induced microglia and incorporated into cerebral organoids. These platforms are intended to better capture human-specific neuroimmune interactions and help clarify how HIV infection, residual viral activity, inflammation, and/or treatment-related factors may contribute to ongoing cognitive and neurological complications despite viral suppression.
The scientific approach encouraged by this announcement centers on recreating key elements of the brain environment in vitro so applicants can probe microglia-driven processes, neuron-glia signaling, inflammatory pathways, synaptic changes, and other neurobiological mechanisms implicated in HAND under cART conditions. By using induced microglia and cerebral organoids generated from patient-derived iPSCs, researchers can potentially compare phenotypes across different donor backgrounds, examine how microglia respond to HIV-related stimuli, and test mechanistic hypotheses about chronic neuroinflammation, neurotoxicity, or disrupted brain homeostasis. The intent is not to run human subject interventions, but to generate foundational mechanistic insights and model systems that can inform later translational work.
This FOA uses the NIH R21 mechanism, which is designed for exploratory or developmental projects that can open new lines of investigation, generate proof-of-concept findings, or establish feasibility for innovative model systems. The opportunity explicitly states that clinical trials are not allowed, meaning the proposed work should not include prospective assignment of human participants to an intervention to evaluate health-related outcomes. The listed award ceiling is $200,000, reflecting the smaller, high-impact, early-stage nature typical of R21 awards. The original closing date for applications was December 18, 2018, and the opportunity was created on September 7, 2018.
Eligibility is broad across U.S.-based organizational types, reflecting NIH norms for many research FOAs. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The announcement also highlights additional eligible categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.
At the same time, the FOA places clear restrictions on foreign involvement. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined in the NIH Grants Policy Statement are not allowed. In practical terms, this means the applicant organization must be domestic and the proposed work must be carried out without foreign components under NIH policy definitions.
Overall, the opportunity is aimed at advancing the field’s ability to model and dissect HAND-related neuropathology in a controlled human-relevant experimental setting, with an emphasis on microglia biology and brain-like organoid systems derived from patient iPSCs, specifically within the context of long-term cART where persistent neurological complications remain a major unmet need.Apply for RFA DA 19 010
- The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279.
- This funding opportunity was created on 2018-09-07.
- Applicants must submit their applications by 2018-12-18. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- Each selected applicant is eligible to receive up to $200,000.00 in funding.
- Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.
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Frequently Asked Questions (FAQs)
What is the title and identifier of this NIH funding opportunity?
This discretionary NIH funding opportunity is RFA-DA-19-010, titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed)."
What health issue or research area is this FOA focused on?
The FOA focuses on HIV-associated neurocognitive disorders (HAND), particularly in the modern treatment era where many people living with HIV are on long-term combination antiretroviral therapy (cART) but may still experience cognitive and neurological complications.
What is the overall purpose of this grant opportunity?
The purpose is to support early-stage, exploratory research that improves understanding of the cellular and molecular mechanisms driving neuropathophysiology in people living with HIV who are receiving long-term cART, using human-relevant in vitro modeling approaches.
What types of research projects does this FOA encourage?
The FOA encourages projects that recreate key elements of the brain environment in vitro to probe mechanisms relevant to HAND, such as microglia-driven processes, neuron-glia signaling, inflammatory pathways, synaptic changes, neurotoxicity, chronic neuroinflammation, and disrupted brain homeostasis in the context of HIV and cART.
What model systems are emphasized in this announcement?
The FOA emphasizes human stem cell-based systems, specifically patient-derived induced pluripotent stem cell (iPSC) lines that can be differentiated into induced microglia and incorporated into cerebral organoids. These systems are intended to capture human-specific neuroimmune interactions more effectively than relying only on animal models or postmortem tissue.
Why does the FOA emphasize iPSC-derived microglia and cerebral organoids?
Because these platforms can better represent human-specific biology and neuroimmune interactions. They can help clarify how HIV infection, residual viral activity, inflammation, and/or treatment-related factors may contribute to ongoing neurological complications even when viral suppression is achieved under cART.
Does this FOA require use of patient-derived iPSC lines?
The FOA specifically highlights patient-derived iPSC lines as a key approach, including differentiation into induced microglia and integration into cerebral organoids to study HAND-related mechanisms.
What kinds of comparisons or experiments are these model systems intended to enable?
The FOA indicates that researchers can potentially compare phenotypes across different donor backgrounds, examine microglial responses to HIV-related stimuli, and test mechanistic hypotheses related to persistent inflammation, neurotoxicity, synaptic or signaling changes, and other pathways relevant to HAND under cART conditions.
What is the NIH activity code/mechanism used for this opportunity?
This FOA uses the NIH R21 mechanism, which is intended for exploratory or developmental research projects that can open new lines of investigation, generate proof-of-concept findings, or establish feasibility for innovative model systems.
What is the maximum award amount mentioned for this R21 opportunity?
The listed award ceiling is $200,000, consistent with the smaller, early-stage, high-impact nature typical of R21 awards.
Are clinical trials allowed under this FOA?
No. The FOA explicitly states "Clinical Trials Not Allowed."
What does "Clinical Trials Not Allowed" mean for applicants?
It means the proposed work should not include prospective assignment of human participants to an intervention to evaluate health-related outcomes. The intent is to generate foundational mechanistic insights and model systems rather than run human subject intervention studies.
Is the goal of this FOA to conduct human subject interventions?
No. The FOA is centered on in vitro, human stem cell-based modeling to generate mechanistic insights that can inform later translational work, rather than conducting interventions in human participants.
What aspect of HIV treatment does this FOA specifically reference?
The FOA specifically references long-term combination antiretroviral therapy (cART) and the need to understand why neurological complications may persist despite viral suppression.
When was this funding opportunity created?
The opportunity was created on September 7, 2018.
What was the original application closing date?
The original closing date for applications was December 18, 2018.
Who is eligible to apply (in general terms)?
Eligibility is broad across U.S.-based organizational types and aligns with common NIH eligibility patterns for research funding, including many government, academic, nonprofit, and for-profit entities (subject to the FOA's foreign involvement restrictions).
Which U.S. government entities are eligible to apply?
Eligible applicants include state, county, and local governments, as well as special district governments.
Are educational institutions eligible to apply?
Yes. Eligible applicants include independent school districts and both public/state-controlled and private institutions of higher education.
Are tribal entities eligible to apply?
Yes. Eligible applicants include federally recognized Native American tribal governments and Native American tribal organizations other than federally recognized tribal governments.
Are housing authorities eligible to apply?
Yes. Public housing authorities and Indian housing authorities are included as eligible applicants.
Are nonprofit organizations eligible to apply?
Yes. Nonprofits with and without 501(c)(3) status (other than institutions of higher education) are eligible.
Are for-profit organizations eligible to apply?
Yes. For-profit organizations (other than small businesses) are eligible, and small businesses are also eligible.
Does the FOA highlight eligibility for specific institution types such as MSIs?
Yes. The FOA highlights eligibility for Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs).
Are faith-based or community-based organizations eligible?
Yes. The FOA explicitly highlights faith-based or community-based organizations among eligible categories.
Are U.S. territories and possessions eligible?
Yes. The FOA includes U.S. territories or possessions among eligible categories.
Are foreign (non-U.S.) organizations eligible to apply?
No. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply under this FOA.
Can a U.S. organization apply if it proposes a non-domestic component?
No. Non-domestic components of U.S. organizations are not eligible.
Are foreign components allowed in the proposed project?
No. Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
In practical terms, what do the foreign involvement restrictions imply?
They imply the applicant organization must be domestic (U.S.-based) and the proposed work must be carried out without foreign components under NIH policy definitions.
What is the scientific gap this FOA is trying to address?
The FOA aims to improve the field's ability to model and dissect HAND-related neuropathology in controlled, human-relevant experimental settings, particularly where persistent neurological complications remain an unmet need despite effective viral suppression under long-term cART.
How does this FOA position its approach relative to animal models or postmortem tissue?
Rather than relying solely on animal models or postmortem tissue, the FOA emphasizes human stem cell-based systems (iPSC-derived microglia and cerebral organoids) to better capture human-specific neuroimmune interactions relevant to HAND.
What types of outcomes or deliverables are most consistent with an R21 under this FOA?
Outcomes consistent with this FOA include feasibility demonstrations, proof-of-concept results, and foundational mechanistic insights enabled by innovative iPSC/microglia/organoid model systems that can support later translational research.
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