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Regulation of protein synthesis by metabolic signals and the circadian clock

Award Number: R15GM129672
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: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Regulation of protein synthesis by metabolic signals and the circadian clock - Project Summary Protein synthesis is a core function of all cells and is the target of multiple signaling pathways that coordinate the translation of mRNAs into proteins in response to exogenous and internal signals. Work from this and other laboratories has highlighted that cyclical signals from the light environment, temperature, metabolic biomarkers, and the circadian clock are integrated to coordinate mRNA ribosome loading on a genome-wide scale. Central in this network is the signaling axis known as the TOR-S6 kinase pathway. It regulates the phosphorylation of several components of the cytosolic translation apparatus including one prominent target on the ribosome, the eS6 protein located at the foot of the small ribosomal subunit. The model system underlying the current project, Arabidopsis thaliana, is not only representative of higher eukaryotes because of the conservation of its TOR-S6K-eS6 signaling channel, but is also an ideal system to study the integration of various cyclical signals in a chronobiological context. The first aim of the project builds on innovative and established molecular, biochemical, and cellular assays to tackle a long-standing question, the biochemical and cellular role of eS6-phosphorylation. Plants in which phosphorylation of eS6 is abolished or otherwise disrupted display at most minor defects in their growth, development, and transcriptome. Therefore, detailed assays of translational fidelity, ribosome biogenesis, translation, and autophagy will be refined and applied to identify the biochemical and cellular scope of eS6 phosphorylation. The second aim is a collaboration with a group of versatile computational biologists under co-investigator Tian Hong. As the cell processes multiple independent circadian signals, it can be predicted theoretically that the precise mode of their integration will lead to new circuit properties including complex waveforms or even ultradian periods. The project will use bioinformatic data mining, mathematical modeling, and wet-lab experimentation to distinguish between competing hypotheses to explain how multiple cyclical signals are integrated with each other.


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 = -$11,383 )
2026	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	2	11/20/2025	COMPETING CONTINUATION	-$11,383
														Subtotal = -$11,383

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	001	2	6/4/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	2	6/3/2024	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $28,575 )
2023	2023	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	004	2	9/11/2023	SUPPLEMENT FOR EXPANSION	$28,575
2023	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	003	2	4/6/2023	COMPETING CONTINUATION	$63,785
2023	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	001	2	11/22/2022	COMPETING CONTINUATION	-$64,077
2023	2018	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	1	11/22/2022	NEW	$64,077
2023	2018	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	002	1	4/6/2023	NEW	-$63,785
														Subtotal = $28,575

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	001	2	11/27/2021	COMPETING CONTINUATION	$64,077
2022	2018	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Biomedical Research and Research Training	000	1	11/27/2021	NEW	-$64,077
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $459,000 )
2021	2021	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	001	2	7/5/2021	COMPETING CONTINUATION	$459,000
2021	2018	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	1	6/28/2021	NEW	$0
														Subtotal = $459,000

Issue Date FY: 2018 ( Subtotal = $437,571 )
2018	2018	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Biomedical Research and Research Training	000	1	6/27/2018	NEW	$437,571
														Subtotal = $437,571

Grand Total All Awards = $913,763

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Regulation of protein synthesis by metabolic signals and the circadian clock

Award Number: R15GM129672

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: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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