Saturday, July 5, 2025 7/5/2025

Single Cell and Single Molecule Technologies for Multiplex Chromatin Interaction Analysis

Award Number: R01HG011253
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/05/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Single Cell and Single Molecule Technologies for Multiplex Chromatin Interaction Analysis - PROJECT SUMMARY Mammalian genome DNA in the cell nucleus is extensively folded to form a complex three-dimensional (3D) chromatin organization, comprising complex and multivalent interplays of chromatin interactions involving DNA, RNA and protein. The 3D genome is arranged so as to facilitate multiple functional interactions, of which our current understanding is limited, but that ultimately serve to regulate gene expression within a cell. An additional layer of complexity is introduced by the observations that the 3D structural and functional interactions of the chromatin folding are not static, but rather dynamic both over time within a given cell, and between cells of the same type. Understanding these complex functional interactions and their variations will be necessary not only for advancing fundamental biological knowledge, but also for providing novel insights into human disease that could lead to new treatment paradigms. The scientific premise of this project is that at any given time, multiple chromatin interactions are occurring at multiple locations through intricate 3D genome organization and that these interactions are mediated, at least in part, by protein and RNA factors. Unfortunately, the limitations of current 3D genome technologies prevent us from precisely revealing this level of functional complexity at the desirable single-molecule resolution. In this proposal we seek to develop a set of single cell and single molecule techniques for studying multiple, complex chromatin interactions involving protein and RNA regulatory factors within the 3D genome organization. The foundation of our strategy lies in a droplet-based and barcode-linked microfluidics system for single cell and single-molecule detection of complex chromatin interactions. We have developed a prototype for analysis of single-molecule chromatin interactions, called ChIA-Drop (Chromatin Interaction Analysis by Droplet sequencing) that works well for a relatively small Drosophila genome. To develop and refine this approach for mammalian cells, and to begin to uncover the interactions that are critical to chromatin topology and genome functions in health and disease, we propose to achieve the following four aims: Aim 1- Based on proof-of-concept of published results for the Drosophila genome we will use human and murine cell lines to make refinements for the larger mammalian genomes. Aim 2 - we will develop a novel dual-indexing strategy (nucleus-specific and chromatin-specific) for single-cell ChIA- Drop analysis (scChIA-Drop), and will apply it to study multiplex chromatin interactions with single-cell and single-molecule resolution in human and in mouse cells. In Aim 3 - we will extend ChlA-Drop to detect multivalent chromatin interactions mediated by protein and RNA factors. Finally, because datasets produced by ChlA-Drop are new data types, in Aim 4 - we will establish robust computational pipelines and tools for decoding chromatin interactions and make them publicly accessible. The development of these advanced ChIA-Drop technologies and tools will enable unprecedented exploration of chromatin interaction biology and advance our understanding of chromatin topology and genome regulatory functions.


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 = -$102,797 )
2024	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Human Genome Research	002	5	2/5/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$8,843
2024	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Human Genome Research	007	5	3/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,172,741
2024	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Human Genome Research	001	5	12/26/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$486,006
2024	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	003	4	2/6/2024	NON-COMPETING CONTINUATION	$10,748
2024	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	006	4	3/14/2024	NON-COMPETING CONTINUATION	-$260,284
2024	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	000	4	12/22/2023	NON-COMPETING CONTINUATION	-$590,708
2024	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	005	3	3/14/2024	NON-COMPETING CONTINUATION	-$839,496
2024	2021	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	004	2	3/14/2024	NON-COMPETING CONTINUATION	-$72,961
														Subtotal = -$102,797

Issue Date FY: 2023 ( Subtotal = $840,244 )
2023	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	000	4	5/18/2023	NON-COMPETING CONTINUATION	$840,244
														Subtotal = $840,244

Issue Date FY: 2022 ( Subtotal = $839,496 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	000	3	6/1/2022	NON-COMPETING CONTINUATION	$839,496
														Subtotal = $839,496

Issue Date FY: 2021 ( Subtotal = $839,326 )
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	001	2	6/11/2021	NON-COMPETING CONTINUATION	$839,326
2021	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	000	1	3/17/2021	NEW	$0
														Subtotal = $839,326

Issue Date FY: 2020 ( Subtotal = $848,800 )
2020	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Human Genome Research	000	1	8/5/2020	NEW	$848,800
														Subtotal = $848,800

Grand Total All Awards = $3,265,069

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Single Cell and Single Molecule Technologies for Multiplex Chromatin Interaction Analysis

Award Number: R01HG011253

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/05/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer