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Mathematical modeling of Drosophila sleep

Award Number: R15GM117507
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: 07/08/2016
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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Mathematical modeling of Drosophila sleep - PROJECT SUMMARY Sleep is a vital process thought to provide a restorative function and is one of the most conserved behaviors in the animal kingdom. Inadequate sleep has been shown to have negative health implications, yet the molecular mechanisms that underlie the sleep process are not well understood. The fruit fly, Drosophila melanogaster, is a genetically tractable model organism with homology to mammalian sleep regulation that can be used to collect a vast amount of experimental data that may associate with the underlying mechanism of sleep and its impact on health. Mathematical modeling of these data can advanced our understanding of sleep-wake dynamics, identify previously unknown influences on the process, and can be used to generate testable hypotheses. Ultimately, by combining the power of Drosophila genetics with mathematical modeling, a better understanding of sleep and wake transition dynamics and how they relate to the biological mechanism that underlies sleep and the aging process can be achieved and possibly inform our understanding of human sleep. The proposed research aims to (1) develop an algorithm that can predict long- and short-lived flies and determine whether molecular mechanisms associated with aging correlate with the predicted short- and long-lived flies, (2) apply novel time series algorithms to characterize the evolution of sleep transitions over the lifetime of a fly, and (3) use a physiological model to determine critical variables and determine links between sleep structure and aging outcomes in Drosophila. Our preliminary data indicate that features derived from sleep architecture in flies over their entire lifespan and are significantly associated with survival time. A significant correlation between sleep architecture and lifespan persists even when data is limited to the first 30 days of a fly's lifespan. Moreover, when data is limited to only the first 30 days of data, there is a significant correlation between sleep architecture and lifespan. We will determine whether flies predicted to be short- or long-lived have differences in markers of aging and whether inducing sleep in these flies helps ameliorate these changes. The second aim focuses on describing an equivalent of Process S in the fly by searching for cyclical behavior associated sleep-wake patterns in circadian rhythm mutant flies. These models have the potential to provide valuable insight into the molecular mechanisms that govern sleep. The third aim will employ the physiologically motivated model to “reverse engineer” sleep parameter estimates in individual flies that can be correlated with health and biochemical changes associated with aging. These estimates will be valuable in gaining an insight into the mechanism that governs the build-up and dissipation of sleep debt and other sleep mechanisms in Drosophila, where standard model building techniques used in mammalian species are not practical. Results from all three aims will provide a better toolkit to address the molecular link between observed sleep parameters and health outcomes.


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: 2022 ( Subtotal = $0 )
2022	2016	UNIVERSITY OF MISSOURI SYSTEM	300 W 12TH ST	ROLLA	MO	65409	PHELPS	USA	Biomedical Research and Research Training	000	1	3/6/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2016	UNIVERSITY OF MISSOURI SYSTEM	300 WEST 12 ST	ROLLA	MO	65409	PHELPS	USA	Biomedical Research and Research Training	001	1	3/10/2021	NEW	$0
2021	2016	UNIVERSITY OF MISSOURI SYSTEM	300 WEST 12 ST	ROLLA	MO	65409	PHELPS	USA	Biomedical Research and Research Training	000	1	2/3/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2016	UNIVERSITY OF MISSOURI SYSTEM	300 WEST 12 ST	ROLLA	MO	65409	PHELPS	USA	Biomedical Research and Research Training	000	1	4/29/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $421,501 )
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	1	7/5/2016	NEW	$421,501
														Subtotal = $421,501

Grand Total All Awards = $421,501

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Mathematical modeling of Drosophila sleep

Award Number: R15GM117507

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: 07/08/2016

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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