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In vivo tracking of bioluminescent markers of circadian rhythms in behaving animals

Award Number: R15GM126545
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: 09/15/2017
PERIOD OF PERFORMANCE END DATE: 09/17/2026

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In vivo tracking of bioluminescent markers of circadian rhythms in behaving animals - Project Summary Circadian rhythms are fundamental in sculpting physiology, and their alignment is essential for optimal health. We have gained deep understanding of the cellular basis as well as the function of the central circadian clock of the suprachiasmatic nuclei (SCN), but we don’t yet understand how the SCN interacts with varied peripheral oscillators, and how these peripheral clocks integrate information from SCN- and non-SCN-inputs to maintain internal alignment as well as entrainment to 24h cycles. Here we will study two peripheral oscillators, the liver and skin. We will develop an animal model for study of the role of these peripheral clocks within the circadian system, to determine their entrainment capabilities. The central hypothesis of this proposal is that peripheral clocks retain some rhythmic capabilities when the SCN central clock is impaired, possibly including photic entrainment. The long- term goal of this research is to understand the inter-dynamics of circadian clocks throughout the mammalian body and, ultimately, discover new tools to lessen the impact of circadian misalignment on health. Our research will first aim to characterize our new skin circadian clock reporter line K14 Cre; DBPKI/+ mice. We will more fully characterize our new mouse line using IVIS imaging, assays, and histology to rigorously determine sources of the bioluminescence recorded. Second, we will aim to test photic entrainment of skin and liver circadian rhythms in vivo in mice with or without brain central clock function. This aim will test the entrainment of skin and liver using methods for long-term circadian bioluminescent reporting from living animals, first in intact mice and then in mice with suprachiasmatic nuclei (SCN) ablation. Third, we will determine if these peripheral tissues show a wider range of entrainment than the central clock. We will test the ability for circadian rhythms of gene expression of K14 Cre; DBPKI/+ and Alb Cre; DBPKI/+ mice to entrain to cycles of varied cycle lengths (“T cycles”), to assess the range of entrainment, as compared with that of locomotor activity, using both intact and SCN-lesion mice. Completion of these studies will dramatically alter our understanding of the mammalian circadian system to include potentially photoreceptive peripheral clocks. The research will be conducted by diverse and engaged undergraduate women, with structured mentoring to encourage continued careers in biomedical science.


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 = $37,099 )
2024	2024	THE TRUSTEES OF THE SMITH COLLEGE	10 ELM ST	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	002	3	7/31/2024	SUPPLEMENT FOR EXPANSION	$37,099
2024	2023	THE TRUSTEES OF THE SMITH COLLEGE	10 ELM ST	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	001	3	1/19/2024	COMPETING CONTINUATION	$70,565
2024	2019	THE TRUSTEES OF THE SMITH COLLEGE	10 ELM ST	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	000	2	1/19/2024	COMPETING CONTINUATION	-$70,565
														Subtotal = $37,099

Issue Date FY: 2023 ( Subtotal = $396,250 )
2023	2023	THE TRUSTEES OF THE SMITH COLLEGE	10 ELM ST	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	000	3	8/24/2023	COMPETING CONTINUATION	$396,250
														Subtotal = $396,250

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	001	2	9/28/2020	COMPETING CONTINUATION	$89,672
2020	2017	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	000	1	9/28/2020	NEW	-$89,672
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $392,394 )
2019	2019	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	001	2	9/18/2019	COMPETING CONTINUATION	$392,394
2019	2017	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	000	1	9/17/2019	NEW	$0
														Subtotal = $392,394

Issue Date FY: 2017 ( Subtotal = $385,288 )
2017	2017	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	000	1	9/13/2017	NEW	$430,256
2017	2017	TRUSTEES OF THE SMITH COLLEGE, THE	1 CHAPIN WAY	NORTHAMPTON	MA	01063	HAMPSHIRE	USA	Biomedical Research and Research Training	001	1	9/15/2017	NEW	-$44,968
														Subtotal = $385,288

Grand Total All Awards = $1,211,031

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In vivo tracking of bioluminescent markers of circadian rhythms in behaving animals

Award Number: R15GM126545

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: 09/15/2017

PERIOD OF PERFORMANCE END DATE: 09/17/2026

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