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Reconstructing the temporal landscape of gene regulation in aging

Award Number: R01AG068579
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Reconstructing the temporal landscape of gene regulation in aging - PROJECT SUMMARY / ABSTRACT The circadian rhythm orchestrates a vast repertoire of biochemical, physiological, and behavioral processes with a 24-hour period. A clock circuit, driven by the oscillatory activation and repression of a set of core clock genes, is present in every cell and regulates the expression of nearly half the genome across all tissues. Abundant epi- demiological evidence links circadian regulation to human health. In particular, sleep and circadian disruption is associated with neurodegeneration, where it is thought to be both a consequence and a risk factor for Alzheimer's disease (AD). As the most common form of dementia in the elderly, AD is rapidly becoming a public health cri- sis, affecting an estimated 5.5M people in the United States (24M world-wide) and is expected to double over the next 20 years. Addressing this crisis requires a deep understanding of disease mechanisms and the identiﬁcation of diagnostic/therapeutic targets. A wealth of existing transcriptomic data, coupled with the development of sophisticated computational tools for temporal reconstruction and analysis, provide an exciting opportunity to identify dysregulation in oscillatory patterns of gene expression associated with aging and AD. We propose to develop novel computational strategies to decipher the oscillatory patterns of gene expression using existing untimed transcriptomic datasets; and to apply them to existing data from studies of AD to identify dysregulation in the oscillatory patterns associated with AD. Our methods address a number of analytical chal- lenges, including the need to reconstruct temporal information from untimed samples; ensuring generalizability and accuracy across different transcriptomic proﬁling technologies; addressing the fact that untimed samples may not span the full day; and identifying changes in complex, non-sinusoidal rhythms. Together, these studies will reveal oscillatory patterns of gene expression associated with aging and Alzheimers disease, and will provide innovative new methods for the circadian analysis of untimed data that can be applied to other phenotypes.


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 = -$857 )
2026	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	5	2/11/2026	NON-COMPETING CONTINUATION	-$857
														Subtotal = -$857

Issue Date FY: 2024 ( Subtotal = $289,900 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Aging Research	000	5	6/21/2024	NON-COMPETING CONTINUATION	$289,900
														Subtotal = $289,900

Issue Date FY: 2023 ( Subtotal = $289,900 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Aging Research	000	4	6/16/2023	NON-COMPETING CONTINUATION	$289,900
														Subtotal = $289,900

Issue Date FY: 2022 ( Subtotal = $289,900 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Aging Research	000	3	7/21/2022	NON-COMPETING CONTINUATION	$289,900
														Subtotal = $289,900

Issue Date FY: 2021 ( Subtotal = $732,855 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Aging Research	000	2	5/28/2021	NON-COMPETING CONTINUATION	$387,178
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Aging Research	001	2	8/17/2021	SUPPLEMENT FOR EXPANSION	$345,677
														Subtotal = $732,855

Issue Date FY: 2020 ( Subtotal = $378,976 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Aging Research	000	1	9/11/2020	NEW	$378,976
														Subtotal = $378,976

Grand Total All Awards = $1,980,674

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Reconstructing the temporal landscape of gene regulation in aging

Award Number: R01AG068579

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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