Tuesday, March 25, 2025 3/25/2025

Administrative Supplement: Enhancing cell-type-specific inference with millions of snRNA-seq and deep learning methods

Award Number: R01AG079291
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is a leading cause of dementia among the elderly and the most prevalent age- related neurodegenerative disease, affecting ~56 million individuals worldwide. Despite of its high heritability (estimates ranging 60-80%) and many genetic variants (residing in tens of loci across the genome) identified from genome-wide association studies (GWAS), our knowledge of the underlying genetic mechanisms remains limited. Uncovering pathophysiological mechanisms underlying AD proves to be highly challenging. To advance our mechanistic understanding of AD, we will first acquire and harmonize various in-house, protected and public data, encompassing bulk and single cell RNA-seq data, GWAS summary statistics, array genotyping and whole genome sequencing data, as well as functional genomic data. We will then analyze them using a suite of computational methods and bioinformatics tools to generate cell-type-specific mechanistic hypotheses. These hypotheses will be validated through experimental technologies. Our validations will be carried out in iPSC-derived neural cells (particularly excitatory neurons and microglia), as well as in iPSC-derived brain organoids involving diverse cell types including neurons, astrocytes, and microglia. In these iPSC-derived cells and organoids models, we will leverage CRISPRi as well as knock-in experimental technologies to perturb the most promising putatively causal regulatory DNA elements, and evaluate the impact by measuring a cascade of molecular and cellular phenotypes including gene expression and AD related physiological phenotypes.


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 = $1,271,062 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	001	3	1/20/2025	SUPPLEMENT FOR EXPANSION	$91,474
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	3	1/14/2025	NON-COMPETING CONTINUATION	$1,179,588
														Subtotal = $1,271,062

Issue Date FY: 2024 ( Subtotal = $1,924,804 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	003	2	6/10/2024	NON-COMPETING CONTINUATION	$132,038
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	001	2	1/22/2024	NON-COMPETING CONTINUATION	$1,188,344
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	002	2	2/21/2024	NON-COMPETING CONTINUATION	$0
2024	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	1	10/31/2023	NEW	$604,422
														Subtotal = $1,924,804

Issue Date FY: 2023 ( Subtotal = $1,356,754 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	1	4/14/2023	NEW	$1,356,754
														Subtotal = $1,356,754

Grand Total All Awards = $4,552,620

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Administrative Supplement: Enhancing cell-type-specific inference with millions of snRNA-seq and deep learning methods

Award Number: R01AG079291

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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