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Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage

Award Number: R00GM140254
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2025
AWARD TERMINATION DATE: 06/09/2025

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Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage - Project Summary DNA recording is a recently developed technology that allows cellular signaling events of interest to be followed over time without removing cells from their physiological context. During a DNA recording experiment, genetically engineered cells expressing the DNA recorder acquire mutations at a “recording locus” as the result of transient cellular events, without perturbing their normal phenotype. At the end of the experiment, once their eventual phenotype is known, cells can be collected and their histories determined by sequencing the recording locus. The work proposed here will lead to a DNA recorder that is not limited, as current technology is, to recording one or two cellular events per experiment, but can record dozens of events in parallel, allowing an unbiased examination of cell history in any context compatible with genetically engineered cells. In this project, the new DNA recorder will be used to study long-term effects for a cell of experiencing significant spontaneous DNA damage. Although DNA damage is very well-studied, it has not previously been possible to follow the rare cells that experience significant spontaneous damage, especially in an in vivo mammalian context. The new DNA recorder will be developed in stages: First, intracellular recording machinery, based on a pre-existing recorder, will be created for a small number of cellular events associated with the DNA damage response. Next, the fidelity of this new recording machinery will be extensively validated in cultured cells and cancer xenografts. Finally, a new recording architecture will be developed and validated, before being introduced into a transgenic mouse to identify how spontaneous DNA damage affects cell fate determination during normal development.


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: 2026 ( Subtotal = -$452 )
2026	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	4	1/14/2026	TERMINATION	-$452
														Subtotal = -$452

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	4	6/9/2025	TERMINATION	$0
2025	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	4	6/9/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $332,236 )
2024	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	4	7/4/2024	NON-COMPETING CONTINUATION	$249,000
2024	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	002	4	9/6/2024	SUPPLEMENT FOR EXPANSION	$80,377
2024	2023	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	3	3/7/2024	EXTENSION WITH OR WITHOUT FUNDS	$2,859
														Subtotal = $332,236

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	3	8/24/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $580,784

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Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage

Award Number: R00GM140254

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2025

AWARD TERMINATION DATE: 06/09/2025

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