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4D functional mapping of glucose metabolism in Living Cells

Award Number: R01GM134086
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: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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4D functional mapping of glucose metabolism in Living Cells - Project Summary/Abstract The objective of this proposal is to elucidate how glucose metabolism (i.e. glycolysis and gluconeogenesis) and mitochondrial metabolism are spatially and functionally (spatiofunctionally) interconnected and dynamically orchestrated in human living cells. Current understanding of the highly enmeshed web of metabolic pathways has been limited in 2D, but cellular metabolism takes place in space and time (i.e. 4D). A number of metabolic pathways are spatially confined into either membrane-bound organelles or membraneless compartments. To understand how metabolic pathways are regulated and networked, it is vital to know how organelles or membraneless compartments are spatially arranged and functionally interplay in 4D. We have recently reported that the cytoplasmic, rate-determining enzymes in glucose metabolism are spatially organized into membraneless compartments in various sizes in human cells. We proposed that they shunt glucose flux to anabolic biosynthetic pathways. More importantly, our preliminary results suggest now that the enzyme compartments, formed by liquid-liquid phase separation (LLPS), might be spatially and functionally linked with mitochondria. Thus, in this proposal, we hypothesize that the enzyme compartments in glucose metabolism are spatially and functionally associated with mitochondria in 4D, by which LLSP plays a role to adapt cellular demands. .We will characterize precise mechanisms of the formation and modulation of the enzyme compartments. In addition, we will reveal how the enzyme compartments of glucose metabolism are functionally and spatially coordinated with the mitochondria and the regulatory mechanisms of their network in living cells. The proposed work will offer new, powerful 4D imaging and analysis approaches to explore novel perspectives of spatiotemporal dynamics of metabolic networks inside cells. This work will provide the fundamental principle of understanding the new class of essential organelles in the cell and will provide a new paradigm to comprehend 4-D map of metabolic networks in living cells.


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 = $0 )
2025	2023	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	5	8/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $320,199 )
2023	2023	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	5	6/26/2023	NON-COMPETING CONTINUATION	$320,199
														Subtotal = $320,199

Issue Date FY: 2022 ( Subtotal = $320,199 )
2022	2022	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	4	6/16/2022	NON-COMPETING CONTINUATION	$320,199
														Subtotal = $320,199

Issue Date FY: 2021 ( Subtotal = $320,199 )
2021	2021	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	3	6/24/2021	NON-COMPETING CONTINUATION	$320,199
														Subtotal = $320,199

Issue Date FY: 2020 ( Subtotal = $320,199 )
2020	2020	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	2	6/18/2020	NON-COMPETING CONTINUATION	$320,199
														Subtotal = $320,199

Issue Date FY: 2019 ( Subtotal = $320,199 )
2019	2019	UNIVERSITY OF MARYLAND BALTIMORE COUNTY	1000 HILLTOP CIR	BALTIMORE	MD	21250	BALTIMORE	USA	Biomedical Research and Research Training	000	1	6/27/2019	NEW	$320,199
														Subtotal = $320,199

Grand Total All Awards = $1,600,995

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4D functional mapping of glucose metabolism in Living Cells

Award Number: R01GM134086

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: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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