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Spatial registration of gene expression in the human brain

Award Number: U01MH122849
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: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Spatial registration of gene expression in the human brain - Project Summary/Abstract Extensive effort has been committed to more fully characterize the human brain transcriptome within and across cell types to better understand changes in RNA expression associated with brain development and aging, developmental or psychiatric brain disorders, and local genetic variation. Large consortia, including psychENCODE, have primarily focused on the molecular profiling of RNA extracted from homogenate/bulk tissue from different brain regions across hundreds of individuals, though single nuclei expression approaches are increasingly being utilized in the second phase of projects. While these differences in signatures across brain regions relate to the unique cell types underlying each region, the specific cell types and their corresponding spatial landscapes are largely unknown. Neurons in different cortical and hippocampal layers show distinct expression patterns, morphology, physiology and patterns of connectivity. Converging evidence suggests that impairments in the formation or maintenance of synapses may be involved in schizophrenia, and studies in the postmortem brains of subjects have pointed to specific cell types and revealed differences in neuronal and synaptic structure that are localized to specific layers, suggesting that genetic risk for schizophrenia may manifest with laminar specificity. In this application, we propose to generate detailed spatial transcriptomics maps of the human DLPFC and hippocampus. These spatial expression maps will be combined with complementary single nuclei sequencing data from the same tissue blocks to develop spatial "registration" approaches that can add spatial information to existing single nuclei datasets in the psychENCODE project. We will combine these spatial and cell type-specific maps to implicate layer- and cell-specific populations in schizophrenia genetic risk and illness state that will be validated using complementary in situ hybridization techniques. These rich spatial transcriptome maps will add another dimension to existing and forthcoming single nuclei RNA-seq datasets in the frontal cortex and hippocampus to further refine the cell types in the human brain and their subsequent dysregulation in debilitating brain disorders.


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: 2024 ( Subtotal = $0 )
2024	2021	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	9/13/2024	NON-COMPETING CONTINUATION	$0
2024	2021	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	2	9/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	9/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $842,796 )
2021	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	002	2	6/22/2021	NON-COMPETING CONTINUATION	$0
2021	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	2	5/7/2021	NON-COMPETING CONTINUATION	$842,796
2021	2020	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	1/5/2021	NEW	$0
														Subtotal = $842,796

Issue Date FY: 2020 ( Subtotal = $904,464 )
2020	2020	LIEBER INSTITUTE, INC.	855 N WOLFE ST	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	4/28/2020	NEW	$904,464
														Subtotal = $904,464

Grand Total All Awards = $1,747,260

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Spatial registration of gene expression in the human brain

Award Number: U01MH122849

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: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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