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Multiscale Analyses of 4D Nucleome Structure and Function by Comprehensive Multimodal Data Integration

Award Number: UM1HG011593
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY The cell nucleus is a heterogeneous organelle that consists of nuclear bodies such as nuclear lamina, speckles, nucleoli and PML bodies. These structures continuously tether and tug chromatin at the small and large scales to synergistically orchestrate dynamic functions in distinct spatio-temporal compartments. A major obstacle to the production of navigable 4D reference maps and relating structure to function in the nucleus remains understanding how these different scales of organization influence each other. In particular, we have a poor understanding of the large-scale genome organization. Growing evidence suggests that such nuclear compartmentalization is causally connected with vital genome functions in human health and disease. However, the principles of this nuclear compartmentalization, its dynamics during changes in cell conditions, and its functional relevance are poorly understood. One lesson from Phase 1 4DN was the huge gap in throughput between imaging methods, that directly measure large-scale multi-landmark relationships, and genomic methods, that aim for whole genome high-resolution maps but are indirect measurements and provide limited information about large-scale compartments. For this 4DN UM1 Center application, we propose to meet these needs through the following Aims: (1) Generate multi-modal imaging and genomic datasets to reveal the structure, dynamics, and function of nuclear compartmentalization; (2) Develop and apply computational tools for data-driven genome structure modeling and integrative analysis of nuclear compartmentalization; (3) Develop an integrative analysis and visualization platform with navigable 4D reference maps of nuclear organization. The combined datasets and results of our proposed approaches will advance our understanding of nuclear compartmentalization, the interwoven connections among different nuclear components, and their functional significance. Our new integrative analysis tools and data-driven predictive models will produce more complete nuclear organization reference maps that integrate large-scale chromosome structure data from live and super-resolution microscopy with multi-modal genomic data including smaller scale chromatin interaction maps and predict functional relationships and dynamic responses. Our navigable reference maps will be publicly accessible through an analysis platform that provides interactive visualization of multiple data types, thus enabling investigators with diverse expertise to simultaneously explore their own data and related datasets/tools and promoting collaborations that will open new horizons into the role of the 4D nucleome in human health and 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 = $0 )
2024	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	000	4	3/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,075,409 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	001	4	9/19/2023	NON-COMPETING CONTINUATION	$2,075,409
2023	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	000	3	6/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,075,409

Issue Date FY: 2022 ( Subtotal = $2,075,409 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	000	3	9/14/2022	NON-COMPETING CONTINUATION	$2,075,409
														Subtotal = $2,075,409

Issue Date FY: 2021 ( Subtotal = $2,075,409 )
2021	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	000	2	9/9/2021	NON-COMPETING CONTINUATION	$2,075,409
														Subtotal = $2,075,409

Issue Date FY: 2020 ( Subtotal = $2,075,409 )
2020	2020	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	000	1	9/22/2020	NEW	$2,075,409
														Subtotal = $2,075,409

Grand Total All Awards = $8,301,636

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Multiscale Analyses of 4D Nucleome Structure and Function by Comprehensive Multimodal Data Integration

Award Number: UM1HG011593

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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