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High-throughput analysis of the effects of gene promoters and chromosomal environments on single-cell gene expression

Award Number: R01HG012304
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Genetically identical cells in the same environment can have large individual differences in gene expression. This “single-cell variability” in gene expression diversifies cell types during development, contributes to chemotherapeutic resistance in cancer cells, and hinders the production of pure cell types in reprogramming protocols. Although single-cell variability is an important property of gene expression in development and disease, the sequence features of promoters and the epigenetic features of chromosomes that predict a gene’s single-cell variability are unknown. To address this gap, we propose to develop a high-throughput technology that measures the single-cell variability of different classes of promoters in diverse chromosomal environments. We propose to integrate transgenes into thousands of locations across the genome and measure the resulting single-cell variability of transgene expression from all locations in parallel. These data will allow us to leverage existing epigenomic maps to identify the features of chromosomal environments that amplify or dampen single-cell variability in gene expression. We propose to apply this technology to multiple cell types and with transgenes carrying diverse promoters. The resulting data will be analyzed with a framework separates the independent contributions of promoters and chromosomal environments to single-cell variability, and also quantifies any interactions between specific promoters and chromosomal environments that impact single-cell variability. Our goal in developing this technology is to understand the properties of the genome that control the single-cell variability of mRNA expression.


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 = $378,235 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Human Genome Research	000	3	1/10/2024	NON-COMPETING CONTINUATION	$378,235
														Subtotal = $378,235

Issue Date FY: 2023 ( Subtotal = $415,406 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Human Genome Research	000	2	1/20/2023	NON-COMPETING CONTINUATION	$373,865
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Human Genome Research	001	2	3/2/2023	NON-COMPETING CONTINUATION	$41,541
														Subtotal = $415,406

Issue Date FY: 2022 ( Subtotal = $410,705 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Human Genome Research	001	1	8/29/2022	NEW	$41,070
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Human Genome Research	000	1	2/16/2022	NEW	$369,635
														Subtotal = $410,705

Grand Total All Awards = $1,204,346

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High-throughput analysis of the effects of gene promoters and chromosomal environments on single-cell gene expression

Award Number: R01HG012304

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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