Opportunity Information: Apply for RFA MH 19 135
The BRAIN Initiative funding opportunity titled "Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)" supports the creation and rigorous validation of next-generation neurotechnology designed for large brains that are closer to humans in structure and function. The core motivation is practical: major progress in treating brain disorders is limited because current methods cannot monitor and manipulate neural circuits in ways that are both safe and minimally invasive. The opportunity is framed around the idea that understanding and eventually correcting dysfunctional brain circuitry will require tools that can reliably target specific cell types and specific circuits, rather than broadly affecting large regions of the brain.
A central theme of the announcement is translation beyond traditional lab models. Over the last decade, neuroscience has produced many powerful tools, especially under the broader BRAIN Initiative, but most were built and optimized for small model organisms such as rodents, fish, and flies. While those systems remain crucial for discovery, they do not fully capture the challenges of delivering and controlling interventions in large, complex brains. This program aims to push tool development into human and non-human primate contexts, where issues like delivery depth, tissue scale, immune responses, distribution patterns, and access constraints become far more relevant. The opportunity emphasizes that tools proven in small animals often need substantial redesign and testing before they can work effectively and predictably in larger brains.
The types of projects encouraged include both genetic and non-genetic approaches that enable precise delivery of genes, proteins, or chemicals to defined neuronal or non-neuronal cell populations, as well as approaches that preferentially engage particular neural circuits. Examples at a high level include improved viral or other vector-based delivery strategies, molecular targeting systems that achieve higher specificity than current methods, and technologies that can label, trace, track, monitor, or manipulate activity in a cell-type or circuit-selective manner. The solicitation also highlights the broader goal of removing key barriers that currently slow or prevent the development of gene therapy-style interventions for the brain, including challenges related to delivery efficiency, targeting accuracy, and safe deployment.
A strong application is expected to go beyond proposing an interesting tool concept and instead lay out a clear plan to validate that the tool actually works as intended in the relevant large-brain setting. Validation is treated as essential, not optional. In practice, that means applicants should propose credible, measurable benchmarks for performance such as specificity (how well the tool hits the intended cell type or circuit), sensitivity (how reliably it detects or manipulates the target), spatial coverage (how well it performs across relevant brain volumes), reproducibility, and safety or tolerability where appropriate. Because the funding announcement is focused on enabling future clinical impact, projects that explicitly address obstacles to eventual clinical translation, such as minimally invasive delivery routes and predictable targeting, fit well within the stated goals.
The award uses a UG3/UH3 cooperative agreement structure and is labeled "Clinical Trial Optional." The UG3/UH3 format is typically designed for milestone-driven programs where an initial phase supports early development and feasibility work (UG3), followed by a second phase that supports expanded development, optimization, and validation (UH3) once predefined milestones are met. The cooperative agreement mechanism also generally implies substantial involvement from NIH program staff during the life of the award, with a more collaborative and milestone-oriented management style than a standard research grant.
Eligibility is broad and includes many organization types across government, academia, nonprofits, and industry. Eligible applicants listed include state, county, city or township 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 and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other categories. The announcement also explicitly notes additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, non-domestic (non-U.S.) entities, regional organizations, and U.S. territories or possessions. This broad eligibility reflects the technical nature of the work and the expectation that meaningful progress may require multidisciplinary teams spanning neurobiology, gene delivery, engineering, chemistry, imaging, computation, and clinical or translational expertise.
Key administrative details in the source information include the agency (National Institutes of Health), the funding opportunity number (RFA MH 19 135), and the funding instrument type (cooperative agreement). The original closing date listed is 2021-05-27, and the opportunity was created on 2018-08-03. Multiple CFDA numbers are associated with the program (93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.313, 93.853, 93.865, 93.866, 93.867), reflecting the multi-institute nature of BRAIN-related funding across NIH.
Overall, the opportunity is best understood as a targeted push to create the kinds of precise, scalable, and validated neurotechnologies that can function in large brains and ultimately support new ways to study and treat brain disorders. The emphasis on cell-type and circuit-level specificity, combined with expectations for real-world validation and attention to delivery barriers, signals that NIH is looking for tools that are not only innovative but also plausibly usable in the complex biological and practical environment that human-focused neuroscience demands.Apply for RFA MH 19 135
- The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.313, 93.853, 93.865, 93.866, 93.867.
- This funding opportunity was created on 2018-08-03.
- Applicants must submit their applications by 2021-05-27. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- 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 of this BRAIN Initiative funding opportunity?
The opportunity is titled "Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)."
What is the main goal of this funding opportunity?
The goal is to support the creation and rigorous validation of next-generation neurotechnology designed for large brains that are closer to humans in structure and function, with an emphasis on tools that can target specific cell types and specific neural circuits.
Why is the focus on cell-specific and circuit-specific tools important?
The announcement frames a practical need: progress in treating brain disorders is limited because current methods cannot monitor and manipulate neural circuits in ways that are both safe and minimally invasive. Tools that can reliably target specific cell types and circuits, rather than broadly affecting large regions, are positioned as essential for understanding and eventually correcting dysfunctional brain circuitry.
What kinds of brain systems are emphasized in this program?
The program emphasizes human and non-human primate contexts, where large-brain challenges like delivery depth, tissue scale, immune responses, distribution patterns, and access constraints are more relevant than in small model organisms.
How is this opportunity different from tool development in rodents or other small model organisms?
Many powerful neuroscience tools were developed and optimized for small organisms (such as rodents, fish, and flies). This opportunity specifically targets translation to large brains, recognizing that tools proven in small animals often require substantial redesign and testing to work effectively and predictably in larger, more complex brains.
What types of approaches are encouraged (genetic vs. non-genetic)?
Both genetic and non-genetic approaches are encouraged. The opportunity supports technologies that enable precise delivery of genes, proteins, or chemicals to defined neuronal or non-neuronal populations, as well as approaches that preferentially engage particular neural circuits.
What are some example project types mentioned at a high level?
Examples include improved viral or other vector-based delivery strategies, molecular targeting systems with higher specificity than current methods, and technologies that can label, trace, track, monitor, or manipulate activity in a cell-type or circuit-selective manner.
Is the program trying to address barriers to brain gene therapy-style interventions?
Yes. The solicitation highlights a broader goal of removing key barriers that slow or prevent development of gene therapy-style interventions for the brain, including challenges related to delivery efficiency, targeting accuracy, and safe deployment.
What does NIH expect regarding validation of the tool?
Validation is treated as essential. A strong application is expected to include a clear plan to validate that the tool works as intended in the relevant large-brain setting, not just an interesting concept.
What kinds of performance benchmarks are expected in the validation plan?
The announcement describes credible, measurable benchmarks such as specificity (how well the tool hits the intended cell type or circuit), sensitivity (how reliably it detects or manipulates the target), spatial coverage (performance across relevant brain volumes), reproducibility, and safety or tolerability where appropriate.
Does this opportunity emphasize clinical translation?
Yes. Because the funding announcement is focused on enabling future clinical impact, projects that address obstacles to eventual clinical translation (such as minimally invasive delivery routes and predictable targeting) align well with the stated goals.
What award mechanism is used (UG3/UH3), and what does it imply?
The award uses a UG3/UH3 cooperative agreement structure. This is typically milestone-driven: an initial UG3 phase supports early development and feasibility work, and a later UH3 phase supports expanded development, optimization, and validation once predefined milestones are met.
What does "cooperative agreement" mean for how the project is managed?
A cooperative agreement generally implies substantial involvement from NIH program staff during the award, with a collaborative, milestone-oriented management style compared to a standard research grant.
What does "Clinical Trial Optional" mean in this announcement?
The opportunity is labeled "Clinical Trial Optional," indicating that proposed work may include a clinical trial component but is not necessarily required, based on the information provided.
Who is the funding agency for this opportunity?
The funding agency is the National Institutes of Health (NIH).
What is the funding opportunity number?
The funding opportunity number is RFA MH 19 135.
What is the funding instrument type?
The funding instrument type is a cooperative agreement.
When was the opportunity created, and what is the closing date listed?
The opportunity was created on 2018-08-03. The original closing date listed is 2021-05-27.
What organizations are eligible to apply?
Eligibility is broad and includes state, county, city or township 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 and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other categories.
Are there additional eligible applicant types explicitly noted?
Yes. The announcement explicitly notes additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, eligible federal agencies, non-domestic (non-U.S.) entities, regional organizations, and U.S. territories or possessions.
Why does the opportunity allow such broad eligibility?
The description ties broad eligibility to the technical and multidisciplinary nature of the work, and the expectation that progress may require teams spanning areas like neurobiology, gene delivery, engineering, chemistry, imaging, computation, and clinical or translational expertise.
What CFDA numbers are associated with this opportunity?
Multiple CFDA numbers are associated: 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.313, 93.853, 93.865, 93.866, and 93.867. The information provided notes this reflects the multi-institute nature of BRAIN-related funding across NIH.
What is the overarching takeaway for applicants?
This opportunity is positioned as a targeted push to create precise, scalable, and validated neurotechnologies that can function in large brains and ultimately support new ways to study and treat brain disorders, with strong emphasis on cell-type and circuit-level specificity, real-world validation, and attention to delivery barriers.
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| BRAIN Initiative: Research Opportunities Using Invasive Neural Recording and Stimulating Technologies in the Human Brain (U01 Clinical Trial Required) Apply for RFA NS 19 001 Funding Number: RFA NS 19 001 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| Developing the Therapeutic Potential of the Endocannabinoid System for Pain Treatment (R01 - Clinical Trial Optional) Apply for PA 18 917 Funding Number: PA 18 917 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| BRAIN Initiative Cell Census Network (BICCN) Specialized Collaboratory on Human and Non-Human Primate Brain Cell Atlases (U01 Clinical Trial Not Allowed) Apply for RFA MH 19 149 Funding Number: RFA MH 19 149 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| BRAIN Initiative Cell Census Network (BICCN) Scalable Technologies and Tools for Brain Cell Census (R01 Clinical Trial Not Allowed) Apply for RFA MH 19 148 Funding Number: RFA MH 19 148 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| Opportunities for Collaborative Research at the NIH Clinical Center (U01 Clinical Trial Optional) Apply for PAR 18 951 Funding Number: PAR 18 951 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $500,000 |
| Pre-application: Opportunities for Collaborative Research at the NIH Clinical Center (X02 Clinical Trial Optional) Apply for PAR 18 950 Funding Number: PAR 18 950 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $500,000 |
| BRAIN Initiative: Research on the Ethical Implications of Advancements in Neurotechnology and Brain Science (R01 Clinical Trial Optional) Apply for RFA MH 19 400 Funding Number: RFA MH 19 400 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $300,000 |
| BRAIN Initiative: Research Resource Grants for Technology Integration and Dissemination (U24 Clinical Trial Not Allowed) Apply for RFA NS 19 006 Funding Number: RFA NS 19 006 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| Small Research Grants for Analyses of Data for the Gabriella Miller Kids First Data Resource (R03 - Clinical Trial Not Allowed) Apply for PAR 19 069 Funding Number: PAR 19 069 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $200,000 |
| Mentored Research Scientist Development Award (Parent K01 - Independent Basic Experimental Studies with Humans Required) Apply for PA 19 084 Funding Number: PA 19 084 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Technology Research Sites (UH2/UH3 Clinical Trial Optional) Apply for RFA AR 19 028 Funding Number: RFA AR 19 028 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $400,000 |
| HEAL Initiative: Back Pain Consortium (BACPAC) Research Program: Mechanistic Research Centers (U19 Clinical Trial Optional) Apply for RFA AR 19 026 Funding Number: RFA AR 19 026 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center (U24 Clinical Trial Not Allowed) Apply for RFA AR 19 027 Funding Number: RFA AR 19 027 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $3,600,000 |
| HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional) Apply for RFA NS 19 018 Funding Number: RFA NS 19 018 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) (UG3/UH3, Clinical Trials Optional) Apply for RFA AT 19 004 Funding Number: RFA AT 19 004 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $500,000 |
| HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed) Apply for RFA TR 19 003 Funding Number: RFA TR 19 003 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: $500,000 |
| HEAL Initiative: Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 1630) (UG3/UH3 Clinical Trial Required) Apply for RFA DA 19 035 Funding Number: RFA DA 19 035 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| HEAL Initiative: Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33 Clinical Trial Optional) Apply for RFA AT 19 006 Funding Number: RFA AT 19 006 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required) Apply for PA 19 127 Funding Number: PA 19 127 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
| Mentored Quantitative Research Development Award (Parent K25 - Independent Clinical Trial Not Allowed) Apply for PA 19 124 Funding Number: PA 19 124 Agency: National Institutes of Health Category: Education, Health, Income Security and Social Services Funding Amount: Case Dependent |
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