Thursday, November 21, 2024 11/21/2024

Extensive multiplexing of protein nucleic-acid interactions to comprehensively study gene expression regulation from chromatin to mRNA degradation

Award Number: R01HG012216
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 Gene expression is tightly controlled at both the RNA and protein level by mechanisms involving chromatin modification, transcriptional regulation, mRNA splicing, processing, translation and degradation. Each of these processes are regulated by nucleic acid-protein interactions (DNA-protein and RNA-protein). Accordingly, there have been tremendous efforts in the scientific community to comprehensively map these interactions, including major international research efforts (e.g. ENCODE, RoadMap Epigenomics) focused on generating reference maps for specific cell types. However, because these binding maps are highly specific for individual cell types, there is a critical need to enable the generation of comprehensive genomic maps for any cell type of interest – including primary cell types, disease models, or other rare cell populations – within an individual lab. This goal remains challenging because existing assays can only map interactions of a single protein at a time and are therefore prohibitively expensive. To address these issues, this proposal will develop a highly innovative technology based on our split-pool barcoding strategy (SPRITE) that maps multiway protein-nucleic acid interactions using high throughput sequencing. The proposed Hi-P technology will be used to establish: (i) a highly multiplexed eCLIP-seq method to map up to hundreds of RNA binding proteins simultaneously to their RNA binding sites, (ii) a highly multiplexed ChIP-seq method to map up to hundreds of DNA binding proteins and histone modifications to their DNA binding sites, and (iii) methods to map these multiple protein-nucleic acid interactions across many samples, among these rare cell types, simultaneously. The proposed technology represents a major advance – it will dramatically increase the scale of existing methods and create new capabilities that are currently not possible. These tools will empower individual researchers to generate detailed genomic datasets in specific biological and disease contexts that are comparable in size and complexity to those generated by the ENCODE project at a tiny fraction of its cost. More generally, we anticipate that these tools will lead to critical new insights into gene regulation and human disease.


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 = $843,813 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	003	3	6/11/2024	NON-COMPETING CONTINUATION	$57,658
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	001	3	1/29/2024	SUPPLEMENT FOR EXPANSION	$69,857
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	002	3	6/5/2024	SUPPLEMENT FOR EXPANSION	$67,657
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	000	3	1/26/2024	NON-COMPETING CONTINUATION	$648,641
														Subtotal = $843,813

Issue Date FY: 2023 ( Subtotal = $793,209 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	003	2	3/8/2023	SUPPLEMENT FOR EXPANSION	$7,762
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	000	2	1/19/2023	NON-COMPETING CONTINUATION	$644,037
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	002	2	3/1/2023	NON-COMPETING CONTINUATION	$71,553
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	001	2	1/25/2023	SUPPLEMENT FOR EXPANSION	$69,857
														Subtotal = $793,209

Issue Date FY: 2022 ( Subtotal = $738,499 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	001	1	5/2/2022	NEW	$73,850
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Human Genome Research	000	1	1/27/2022	NEW	$664,649
														Subtotal = $738,499

Grand Total All Awards = $2,375,521

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Extensive multiplexing of protein nucleic-acid interactions to comprehensively study gene expression regulation from chromatin to mRNA degradation

Award Number: R01HG012216

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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