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Oscillatory gene expression and the maintenance of temporal patterning

Award Number: R01GM117406
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: 03/01/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Oscillatory gene expression and the maintenance of temporal patterning - Project Abstract: Developmental gene regulation is a multidimensional problem where signals converge to generate patterns of transcription at the proper location (spatial regulation) and correct time (temporal regulation). An equally important feature of this regulatory process involves generating the correct amount of transcription during development as many key regulatory genes function in dosage sensitive manners where too much or too little expression can lead to developmental defects or disease. At present, we have only a primitive understanding about how the transcriptional output of developmentally regulated genes is established. Experiments outlined in this proposal aim to directly address this problem by employing an in vivo imaging system in C. elegans larva where GFP molecules are directly tethered to nascent RNAs while they are being actively transcribed in the nucleus. This new platform enables us to directly quantify and model the real-time expression dynamics that ultimately dictate transcriptional output of individual genes throughout development. In Aim 1, we will use this system to dissect the mechanisms by which two transcription factors, BLMP-1 and LIN-42, modulate features of transcriptional bursting (including burst frequency, duration, and amplitude) to tune transcriptional levels of key microRNAs (including lin-4 and let-7) that dictate sequential patterns of cell fate specification. We will then probe the genomic and molecular mechanisms that BLMP-1 employs to prime future transcription by remodeling chromatin accessibility near target gene loci. In the final Aim, we will characterize the physical and functional interactions between LIN-42 and several conserved nuclear hormone receptors (NHR-23RORγ and NHR-85Rev- erbβ) that mediate temporal aspects of lin-4 and let-7 transcriptional activation. This avenue of research will reveal the principles by which chromatin remodeling and its impact on modulating the transcriptional output of cyclically expressed genes ensures the precision and robustness of cell fate specification during 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: 2025 ( Subtotal = $415,296 )
2025	2025	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	9	5/2/2025	NON-COMPETING CONTINUATION	$415,296
														Subtotal = $415,296

Issue Date FY: 2024 ( Subtotal = $415,296 )
2024	2024	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	8	5/9/2024	NON-COMPETING CONTINUATION	$415,296
														Subtotal = $415,296

Issue Date FY: 2023 ( Subtotal = $415,296 )
2023	2023	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	7	4/28/2023	NON-COMPETING CONTINUATION	$415,296
														Subtotal = $415,296

Issue Date FY: 2022 ( Subtotal = $646,507 )
2022	2022	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	002	6	9/1/2022	SUPPLEMENT FOR EXPANSION	$231,950
2022	2022	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	001	6	6/23/2022	COMPETING CONTINUATION	$415,296
2022	2020	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	5	6/14/2022	NON-COMPETING CONTINUATION	-$739
														Subtotal = $646,507

Issue Date FY: 2020 ( Subtotal = $403,200 )
2020	2020	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	001	5	3/2/2020	NON-COMPETING CONTINUATION	$40,320
2020	2020	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	5	1/7/2020	NON-COMPETING CONTINUATION	$362,880
														Subtotal = $403,200

Issue Date FY: 2019 ( Subtotal = $403,200 )
2019	2019	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	4	12/12/2018	NON-COMPETING CONTINUATION	$403,200
														Subtotal = $403,200

Issue Date FY: 2018 ( Subtotal = $527,880 )
2018	2018	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	3	12/18/2017	NON-COMPETING CONTINUATION	$362,880
2018	2018	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	001	3	5/14/2018	NON-COMPETING CONTINUATION	$40,320
2018	2018	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	002	3	8/15/2018	SUPPLEMENT FOR EXPANSION	$124,680
														Subtotal = $527,880

Issue Date FY: 2017 ( Subtotal = $403,200 )
2017	2017	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	2	12/22/2016	NON-COMPETING CONTINUATION	$362,880
2017	2017	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	001	2	8/8/2017	NON-COMPETING CONTINUATION	$40,320
														Subtotal = $403,200

Issue Date FY: 2016 ( Subtotal = $403,200 )
2016	2016	COLD SPRING HARBOR LABORATORY	BUNGTOWN ROAD	COLD SPRING HRBR	NY	11724		USA	Biomedical Research and Research Training	000	1	2/24/2016	NEW	$403,200
														Subtotal = $403,200

Grand Total All Awards = $4,033,075

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Oscillatory gene expression and the maintenance of temporal patterning

Award Number: R01GM117406

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: 03/01/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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