Key Dates

None

National Institute of Mental Health (NIMH)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders and Stroke (NINDS)

National Center for Complementary and Integrative Health (NCCIH)

The National Institute of Mental Health (NIMH), along with the NIH Institutes and Centers participating in the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, intends to issue a Funding Opportunity Announcement (FOA) to support the creation of Centers for accelerated engineering and optimization of high-impact, molecular technologies to monitor and/or manipulate brain cell activity in experimental animals. The Centers will produce high-impact molecular probes such as, but not limited to, fluorescent protein indicators of neuronal state variables (e.g., intracellular calcium, membrane voltage, released neurotransmitters/neuromodulators, etc.), molecular integrators of neural activity, optogenetic, chemogenetic, sonogenetic, magnetogenetic actuators, and activity-dependent molecular switches. The Centers will be part of the BRAIN Initiative Armamentarium project, whose goal is to generate tools to specifically access, manipulate, and monitor brain cell types across multiple species. Technology optimization is sought for existing tools for brain cell monitoring or manipulation that are beyond the proof-of-concept stage and that can be delivered selectively as payloads to cell types using newly developed brain cell access reagents. Each Molecular Payloads Center is expected to integrate: (1) sufficiently scaled molecular engineering, (2) in vivo validation of improvements seen in engineering assays in intact brains of experimental animals, (3) benchmarking throughout the technology development against existing best-in-class tools, and (4) adaptation of tools into easily produced and applied formats for neuroscience users. Molecular Payloads Centers may also include optional demonstration experiments that establish groundbreaking capabilities of improved molecular tools in vivo. Close interaction will be fostered between technologists and neurobiologists in a research consortium including tool developers funded by other Armamentarium FOAs for brain cell access reagents. The Armamentarium consortium will promote rigorous technology design, benchmarking, validation, and distribution of monitoring and/or manipulation tools and associated brain cell access reagents.

This Notice is being provided to allow potential applicants sufficient time to develop the appropriate collaborations for responsive projects.

The FOA is expected to be published in December 2022 with an expected application due date in June 2023 and the earliest start date in April 2024.

The FOA will use the UM1 activity code (cooperative agreement). Details of the planned FOA are provided below.

Background

The FOA is related to the transformative project, "A Cell Type-Specific Armamentarium for Understanding Brain Function and Dysfunction," described in the "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" report of the Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.0.

The BRAIN Initiative Armamentarium project is a large-scale effort with a goal to generate and implement methods to specifically access, manipulate, and monitor brain cell types across multiple species. With the emergence of more detailed brain cell censuses, there is now the possibility to monitor and manipulate "brain cell function and resolve questions of cause and effect between cell types, their functional outputs, and illnesses of the brain" according to the BRAIN Initiative 2.0 report. Developing robust technologies to access defined cell types is supported through various BRAIN Initiative Armamentarium FOAs, including RFA-MH-20-556 and RFA-MH-21-180. This new FOA will join the Armamentarium project with the creation of Molecular Payloads Centers.

Objectives

The FOA will support the accelerated engineering and optimization of high-impact, molecular technologies to monitor and/or manipulate brain cell activity in experimental animals (e.g., fluorescent protein indicators of neuronal state variables, molecular integrators of neural activity, optogenetic, chemogenetic, sonogenetic, magnetogenetic actuators, activity-dependent molecular switches). In particular, tools are sought that can be delivered selectively as payloads to cell types using new brain cell access reagents produced by investigators in the field who are focused on such vectors. In the future, combining scaled-up, cell type-selective reagents produced under other Armamentarium brain cell type-selective access FOAs (RFA-MH-20-556, RFA-MH-21-180) with optimized molecules for monitoring and/or manipulating neural activity developed under this payloads optimization FOA promises to open new frontiers in neuroscience. Reproducibility and reliability of molecular access, monitoring, and perturbation of circuit components will enable the study of neural coding, computation, storage, and retrieval at cellular resolution. The compatibility of such technologies with recording and modulation of targeted cell types in intact brains of animals will enable the dissection of neural circuits through correlation or causal manipulation of circuit component activity with behaviors. Ultimately, a dynamic picture of neural activity and functional circuits will provide insights into how to diagnose, treat, and prevent human brain disorders in the future.

The "BRAIN 2025: A Scientific Vision" report enumerated several core principles, including that "[n]ew methods should be critically tested through iterative interaction between tool‐makers and experimentalists. After validation, mechanisms must be developed to make new tools available to all." The FOA will foster close interaction between technologists and neurobiologists in a research consortium. The Armamentarium consortium will promote rigorous technology design, benchmarking, validation, and distribution.

Each Molecular Payloads Center is expected to integrate: (1) large-scale molecular engineering, (2) in vivo validation of improvements seen in engineering assays in intact brains of experimental animals, (3) benchmarking throughout the technology development against existing best-in-class tools, and (4) adaptation of tools into easily produced and applied formats for neuroscience users. It is possible that the optimization efforts could result in optional demonstration experiments that establish groundbreaking capabilities of improved molecular tools in vivo.

Plan for Enhancing Diverse Perspectives (PEDP)

The FOA will require a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application. Applicants are strongly encouraged to view the available PEDP guidance material as described in NOT-MH-21-310 and the BRAIN Initiative webpage on the PEDP.

TBD

Applications are not being solicited at this time. 

Please direct all inquiries to:

Douglas S. Kim, Ph.D.

National Institute of Mental Health (NIMH)

301-827-6463

[email protected]