Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed) | PAR 24 024

Frequently Asked Questions (FAQs)

What is this funding opportunity?

This opportunity is a National Institutes of Health (NIH) R01 funding announcement: PAR-24-024, titled "Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed)." It supports basic and mechanistic neuroscience research focused on how well-supported risk factors for complex brain disorders impact neural function at molecular, cellular, and circuit levels.

What is the main scientific focus of PAR-24-024?

The emphasis is on biological mechanisms that sit between risk and disease. Projects should explain how high-confidence risk factors (genetic and/or environmental) change intracellular processes, cell-to-cell interactions, and circuit properties in ways that are informative for understanding disease-relevant neurobiology. The goal is not to build a complete disease model, but to isolate and explain the neurobiological impact of risk factors.

What does NIH mean by "complex brain disorders" in this FOA?

In this context, "complex" can refer to (1) risk that arises from many contributing influences (for example, polygenic architecture and/or environmental exposures), and/or (2) disorders involving widely distributed brain functions rather than a single localized deficit.

What kinds of risk factors are in scope?

The FOA is oriented around well-supported (high-confidence) risk factors. These can be genetic risk signals, environmental exposures, or combinations of influences, as long as the application clearly links the chosen risk factor(s) to mechanistic work on neural function at molecular, cellular, and/or circuit levels.

What types of studies are encouraged?

Both hypothesis-generating and hypothesis-testing studies are encouraged. Hypothesis-generating approaches can include unbiased discovery methods (such as omics, screening, or broad mapping). Hypothesis-testing approaches can include mechanistically targeted experiments designed to establish how a risk factor alters specific pathways, cell states, interactions, or circuit properties.

What biological levels should projects address?

Projects are expected to focus on intracellular, transcellular, and circuit substrates of neural function. Examples include: which molecular pathways or cellular components are altered by a risk factor; how changes propagate across cells (for example through neuron-glia interactions, synaptic signaling, trophic support, or immune-related signaling); and how these changes influence defined circuit properties such as connectivity, excitation/inhibition balance, plasticity rules, or developmental trajectory.

Are circuit-level questions allowed even if the work is mainly molecular or cellular?

Yes. The FOA explicitly includes circuit substrates of neural function and provides examples of circuit properties (connectivity, excitation/inhibition balance, plasticity rules, developmental trajectory). Applications can focus more heavily on one level while still connecting results to mechanistic understanding across levels where appropriate.

Are behavioral experiments required?

No. Behavioral paradigms can be included when they help interpret molecular, cellular, or circuit mechanisms, but behavior is not required and is not expected to be the centerpiece of the work.

Does this FOA support building full disease models?

No. A key boundary is that applications should not be designed primarily to "model the disorder" as a whole. The intent is to isolate and explain the neurobiological impact of individual or combined risk factors and the biological processes those factors affect, rather than constructing an end-to-end model of a disorder.

Are clinical trials allowed under this FOA?

No. The FOA title states "Clinical Trial Not Allowed," and applications should avoid clinical trial designs. Proposed work should remain in mechanistic and preclinical experimental research.

What experimental systems and platforms are acceptable?

The FOA allows in vivo, in situ, and in vitro paradigms. Acceptable platforms include model organisms and human cell-based systems such as iPSC-derived neurons/glia, brain organoids, and other tractable experimental systems, as long as the work is clearly aimed at mechanism.

Can applicants use human cell-based systems like iPSCs or organoids?

Yes. Human cell-based systems are explicitly described as acceptable platforms, including iPSC-derived neurons/glia and brain organoids, provided the application is centered on mechanistic understanding of risk-factor effects.

What kinds of cell-to-cell or transcellular mechanisms are of interest?

The FOA highlights transcellular propagation of risk-factor effects, including examples such as neuron-glia interactions, synaptic signaling, trophic support, and immune-related signaling. The broader expectation is that applicants explain how molecular or cellular changes influence other cells and feed into circuit-level function.

What are the expectations around sharing and dissemination?

A major priority is dissemination and standardization so results can be broadly reused. Applicants are encouraged to share experimental paradigms, identified component pathways, and defined biological processes in enough detail to meaningfully enrich community or federated data resources.

Does the FOA mention any specific data/knowledge standards or frameworks?

Yes. The FOA points to practices aligned with the Gene Ontology, the Synaptic Gene Ontology, and FAIR data informatics principles. The intent is to make mechanistic findings computable, interoperable, and easier to integrate across studies.

What is the broader goal NIH is trying to achieve with this program?

The bigger-picture goal is to narrow the gap between risk-factor discovery (for example from human genetics or epidemiology), the underlying biology that explains those risk signals, and eventual identification of therapeutic targets. The FOA is positioned as a mechanism-focused bridge between risk signals and actionable biology.

What funding mechanism is used?

The funding instrument is an NIH research project grant (R01).

What is the CFDA number and category associated with this opportunity?

The listing associates the opportunity with CFDA 93.242 and places it in the health category.

Is this opportunity mandatory or discretionary?

It is listed as discretionary.

What is the closing date shown in the listing?

The original closing date shown is 2026-09-07.

Is there an award ceiling or an expected number of awards provided?

No. The provided listing does not specify an explicit award ceiling or the expected number of awards. In situations like this, applicants typically consult the full FOA and any NIH institute-specific guidance for budget expectations, paylines, and program priorities.

Who is eligible to apply?

Eligibility is broad. It includes many U.S. organizations and government entities (state, county, city/township, special district governments, and independent school districts), public and state-controlled institutions of higher education, private institutions of higher education, nonprofits with or without 501(c)(3) status (other than universities), public housing authorities/Indian housing authorities, federally recognized Native American tribal governments, and other Native American tribal organizations.

Are for-profit organizations eligible?

Yes. The listing allows for-profit organizations (other than small businesses), small businesses, and other eligible applicants.

Are minority-serving institutions and other specific institution types highlighted as eligible?

Yes. The announcement highlights additional eligible applicant categories including HBCUs, Hispanic-serving institutions, AANAPISIs, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and faith-based or community-based organizations.

Are U.S. territories, possessions, and federal agencies eligible?

Yes. The eligibility section indicates eligible federal agencies and U.S. territories or possessions are included.

Are non-U.S. (foreign) organizations eligible?

Yes. The listing indicates non-U.S. (foreign) organizations and regional organizations are eligible, reflecting an intent to support a diverse applicant pool and a wide range of institutional settings.

What should applicants avoid when framing their proposed aims?

Based on the boundaries described, applicants should avoid framing the project primarily as building a full disorder model and should avoid clinical trial designs. The proposed work should remain focused on mechanistic understanding of how risk factors alter molecular, cellular, and circuit substrates of neural function.

What kind of outputs does NIH want from funded projects?

The FOA emphasizes well-annotated, shareable outputs: experimental paradigms described in reusable detail; identified component pathways; and defined biological processes that can enrich community or federated data resources and fit with computable knowledge frameworks (for example, ontology-aligned representations and FAIR-oriented practices).