Key Dates

NOT-MH-21-261 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Cell Atlas Network (BICAN): Specialized Collaboratory on Human, Non-human Primate, and Mouse Brain Cell Atlases (U01 Clinical Trial Not Allowed);

NOT-MH-21-262 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Cell Atlas Network (BICAN): Coordinating Unit of Biostatistics, Informatics, and Engagement (CUBIE) (U24 Clinical Trial Not Allowed)

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 a group of large-scale Comprehensive Centers that will adopt scalable technology platforms and streamlined sampling strategies and assay cascade to create comprehensive and highly granular brain cell atlases of human and non-human primates with an emphasis on human. The Centers are expected to characterize all brain cell types (neurons, glia, and other non-neuronal cells) at high-resolution. The overarching goal of the BICAN is to build reference brain cell atlases that will be widely used throughout the research community, providing a molecular and anatomical foundational framework for the study of brain function and disorders.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The FOA is expected to be published in July, 2021 with an expected application due date in November, 2021.

This FOA will utilize the UM1 activity code. Details of the planned FOA are provided below.

Background

This FOA is related to the recommendations by the Advisory Committees to the NIH Director as described in Priority Area 1. Discovering Diversity and Priority Area 2. Maps at Multiple Scales in BRAIN 2025 Report, and the transformative project, The Human Brain Cell Atlas, in The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures.

The BRAIN 2025 Report envisioned a systematic census of neuronal and glial cell types in multiple mammalian species. The NIH BRAIN Initiative has implemented this vision by successfully completing a 3-year pilot phase (2014-2017), followed by launching a 5-year phase 2 (2017-2022) BRAIN Initiative Cell Census Network (BICCN) with an emphasis on mouse brain. The BICCN has applied a set of leading edge single-cell approaches to characterizing molecular signatures, anatomical phenotypes, and functional properties of brain cell types, and rapidly disseminated the cell census data to the public. The BICCN is on track to complete a comprehensive cell census spanning the entire adult mouse brain, as well as to set stage for large-scale cell atlas research in human and non-human primate (NHP) brains. Advances in single-cell transcriptomic and epigenomic profiling, anatomical mapping at cellular resolution, and other approaches have proven to be powerful and scalable. In recognition of these advances and the opportunities they enable, the BRAIN Initiative has recently issued a Notice to increase the funding and number of awards available for RFA-MH-21-140, "BRAIN Initiative Cell Census Network (BICCN) Scalable Technologies and Tools for Brain Cell Census; together these events help set the stage toward creating the Human Brain Cell Atlas. At this time, the BRAIN initiative cell census program is looking to establish the BICAN to broaden and deepen the systematic cell census and atlas efforts with a new emphasis on human brain.

The BICAN will be made up of five highly interactive components with complementary roles as follows:

1. Comprehensive Centers on Human and Non-human Primate Brain Cell Atlases (UM1) (NOT-MH-21-260)

2. Specialized Collaboratories on Human, Non-human Primate, and Mouse Brain Cell Atlases (U01) (Companion, see NOT-MH-21-261)

3. Coordinating Unit for Biostatistics, Informatics, and Engagement (CUBIE) (U24) (Companion, see NOT-MH-21-262)

4. BRAIN Initiative Data Archives (R24) (RFA-MH-20-600)

5. Scalable Technologies and Tools Projects (R01) (RFA-MH-21-140)

Research Objectives

Applicants are expected to propose large-scale and robust data production pipelines, using advanced omics and/or imaging technologies and assay platforms to characterize brain cell molecular signatures (transcriptome, epigenome, proteome, etc.) and/or anatomical phenotypes (spatial omics, cell distribution, morphology, connectivity, cytoarchitecture, etc.), annotating cell heterogeneity in all brain regions with focus on one or more age groups across lifespan. In addition, applicants may propose limited functional characterization of molecularly and anatomically identified brain cell types and describe brain cell atlas use cases in context of disease-focused studies as appropriate.

Comprehensive Centers are expected to work closely together with Specialized Collaboratories to:

• establish human brain specimen acquisition and processing pipeline to ensure adequate human brain donor diversity (age, sex, ancestry), high quality of brain specimens, and proper medical and anatomical annotations;
• optimize tissue processing, dissection and microdissection; streamline sampling strategies to achieve both broad coverage of all brain cell types and deep characterization of rare cell types in order to generate anatomically annotated high granular brain cell atlases;
• adopt and improve scalable technology platforms and iterative assay cascade to achieve high production and cost efficiency;
• generate large-scale molecular and anatomical data in systematic and cost-effective manner aiming to meet Complete, Accurate, and Permanent (CAP) criteria;
• process and rapidly share verified raw data, perform data analysis, visualization, and mapping to common coordinate systems;
• work closely with other BICAN projects to synergize and harmonize the data generation and analysis workflows, and establish data standards for joint analysis and publications;
• use the brain cell atlas data to provide new insights into molecular and cellular organizational rules underlying brain circuits and function, individual variabilities, and changes across the lifespan;
• coordinate with brain disease-focused research projects to quantitatively characterize and map genetic risk variants and QTLs (quantitative trait loci) to cell types and circuits;
• coordinate with brain technology and structure and function research projects (e.g., cell type-specific armamentarium, large-scale functional recordings, theories and models supported by the BRAIN Initiative; Human Connectome Project, etc.) to link and map molecular and anatomical atlases with brain function.

Applicants must provide a detailed description on Human Brain Specimen Acquisition, Processing, and Characterization to be shared across BICAN if funded, which includes but is not limited to:

• brain specimen donor age, sex/gender, ancestry,
• medical records,
• inclusion and exclusion criteria used for the brain tissue acquisition,
• tissue collection, processing, and preservation methods used,
• photo documentation of brain sections,
• quality assurance and quality control metrics and parameters that define sample quality for the proposed research, e.g., Post-mortem Interval (PMI), RNA Integrity Number (RIN), histology, pilot single-cell analysis datasets, etc.

Applicants are expected to team up with one or more established brain sources (e.g., NIH NeuroBioBank) to work towards establishing a collection of neurotypical brain specimens that may serve as control samples in the brain disorders research, which will adequately cover human demographic diversity of the United States, including all age groups across the life span (infancy, childhood, adolescence, adulthood, and seniorhood), sex/gender, race, and ethnicity. Applicants are expected to pursue broad donor consent for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data.

BICAN is expected to develop and establish a sampling strategy with a broad coverage of brain structures/regions and cell types of whole brain and adequate depth and resolution in characterizing rare cell types. Applicants are expected to provide a detailed Assay Sampling Plan on assay sampling strategy and workflow and address what level of granularity and resolution will be achieved in anatomically distinct brain regions. The Assay Sampling Plan is expected to list the assays to be performed, the numbers of samples (e.g., brain structures/regions, cell types, species, sex, age groups/developmental stages, ancestry, etc.) to be analyzed, and the iterative assay design. The purpose is to establish a Network with complementary capabilities and capacities toward generating comprehensive and complete brain cell atlases.

Research objectives must emphasize human brain studies as a main focus. Applications including additional species beyond human and NHPs must provide very strong scientific and cost justifications. Applications focusing on mouse brain studies should be submitted to the companion BICAN FOA on Specialized Collaboratories (U01).

Applications are not being solicited at this time.

Please direct all inquiries to:

Yong Yao, Ph.D.

National Institute of Mental Health (NIMH)

301-443-6102

yyao@mail.nih.gov