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Functionally guided adult whole brain cell atlas in human and NHP

Award Number: UM1MH130981
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/22/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Functionally guided adult whole brain cell atlas in human and NHP - Progress in treating brain disorders has been frustratingly slow, in large part due to the extraordinary complexity of the human brain and its inaccessibility to study. Remarkable advances in technologies for studying individual cells, most notably single cell genomics, have revolutionized the study of complex nervous tissues and have been used to map cellular diversity across the entire mouse brain with cell types defined by their specific patterns of gene usage and gene regulatory mechanisms. These highly scalable methods have been successfully applied to brain tissue from human and other species and are ready to be applied to whole brains from humans and non-human primates. A major challenge with studying the human brain is bridging fields and scales from functional MRI and macroscale connectomics to histological, cellular and molecular analyses. Bridging these domains is essential to creating a transformative new cell atlas that will describe the cellular and molecular underpinnings of the functional organization of the human brain. An important recent development from single cell genomic analysis is that cell types can be aligned across species and are highly conserved across mammals from mice to humans, although more similar in evolutionarily closer primates than in rodents. This finding amplifies the value of primate species in helping to understand human brains and infer cellular properties that cannot be measured in humans. The current proposal brings together a unique team of world leaders to tackle the challenge of creating a new human and non-human primate cell atlas linked to functional brain architecture. Single cell transcriptomic, epigenomic and spatial transcriptomics will be used to classify and spatially map cell types across the entire human, macaque and marmoset brain, sampling based on brain maps derived from structural and functional imaging. Function-localizing fMRI in macaques will allow the direct analysis of cellular correlates of functional topography. Advances in spatial transcriptomics will allow an unprecedented whole primate brain map of cell types. Unique access to macaque tissues for analysis of cellular anatomy and physiology allows the characterization of molecularly-defined cell types in many brain regions. Similar techniques will be applied to living neurosurgically-derived human brain tissues, coupled with enhancer-AAV based tools to allow selective genetic labeling of cell types. Finally, profiling regions central to perception, behavior and mood across many individuals and diverse mammals will link genetic, environmental and evolutionary factors to cellular variation. The outcome of these efforts will produce a new reference classification for cell types across the whole human and NHP brain, spatial maps of molecularly defined cell types, and phenotypic characterization of fundamental brain cell types. The classification will align homologous cell types from mice, marmosets, macaques and humans, allowing inference and comparison of cellular properties across species. Furthermore, data will be aligned in common coordinate frameworks, allowing creation of new atlases spanning structural, functional, cellular and molecular information. All data and analyses will be distributed to the research community, including a formal cell ontology of cell types across species and visualization tools for broad community access.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $17,262,570 )
2025	2025	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	003	4	8/4/2025	NON-COMPETING CONTINUATION	$17,262,570
2025	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	002	3	4/25/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	001	3	4/25/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	000	3	4/25/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $17,262,570

Issue Date FY: 2024 ( Subtotal = $17,549,442 )
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	004	3	9/5/2024	SUPPLEMENT FOR EXPANSION	$85,677
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	005	3	9/12/2024	NON-COMPETING CONTINUATION	$0
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	001	3	7/2/2024	NON-COMPETING CONTINUATION	$17,255,818
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	002	3	7/26/2024	SUPPLEMENT FOR EXPANSION	$117,797
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	003	3	8/20/2024	SUPPLEMENT FOR EXPANSION	$90,150
2024	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	000	2	5/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $17,549,442

Issue Date FY: 2023 ( Subtotal = $17,379,729 )
2023	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	004	2	8/8/2023	NON-COMPETING CONTINUATION	$0
2023	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	003	2	7/1/2023	NON-COMPETING CONTINUATION	$17,379,729
2023	2022	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	002	1	5/16/2023	NEW	$0
2023	2022	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	001	1	11/18/2022	NEW	$0
2023	2022	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	000	1	10/19/2022	NEW	$0
														Subtotal = $17,379,729

Issue Date FY: 2022 ( Subtotal = $22,864,467 )
2022	2022	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	000	1	8/19/2022	NEW	$22,864,467
														Subtotal = $22,864,467

Grand Total All Awards = $75,056,208

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Functionally guided adult whole brain cell atlas in human and NHP

Award Number: UM1MH130981

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/22/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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