Sunday, May 19, 2024 5/19/2024

Investigating the partitioning of glucose to lipids versus respiration, an undergraduate-based approach to dissect a pivotal point of metabolic control

Award Number: R15GM100376
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

ABSTRACT A pivotal point in cellular resource allocation is the point at which glycolytic intermediates are partitioned to lipid biosynthesis versus respiration. For example, hyperlipidemia occurs when cells favor lipid biogenesis and is a major risk factor for cardiovascular disease (CVD) including coronary heart disease, heart attack and stroke, the number one causes of death in the United States. PAS kinase is a serine-threonine protein kinase that is a key regulator of this pivotal point in glucose allocation. PAS kinase-deficient mice (PASK-/-) placed on a high-fat diet or a high-fat high-sugar diet are resistant to liver triglyceride accumulation and display increased whole animal as well as cellular respiration rates when compared to their wild type littermates. Liver triglyceride accumulation and altered metabolic rate are two primary risk factors in the development of CVD as well as related diseases such as type II diabetes. We have recently identified two PAS kinase substrates that may explain its regulation of this pivotal point in metabolism, upstream stimulatory factor 1 (USF1) and Ataxin-2. Our hypothesis is that PAS kinase regulates the pivotal point of partitioning glucose to lipid versus respiratory pathways through phosphorylation of its substrates USF1 and Ataxin-2. USF1 is a transcription factor that directly regulates fatty acid synthase and human mutations in USF1 are associated with familial hypercholesterolemia. PAS kinase phosphorylates and inhibits USF1 in yeast. This phosphorylation leads to decreased respiration and increased lipid biosynthesis. Ataxin-2, on the other hand, associates with and sequesters mRNA and proteins to stress granules, regulating cellular metabolism through their inhibition. PAS kinase-dependent phosphorylation of Ataxin-2 activates the protein by increasing its localization to stress granules in yeast. The focus of this proposal is to further characterize the effects of PAS kinase-dependent phosphorylation on the function of USF1 and Ataxin-2 in yeast and mammalian systems. Our long term goal is to increase our understanding of the regulation of central metabolism while training undergraduates in scientific research, thereby identifying novel targets for the treatment of metabolic disease. Throughout this proposal we will use the genetic and biochemical tools of yeast to investigate diseases for which most undergraduates have a personal connection to, namely hyperlipidemia and diabetes.


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: 2023 ( Subtotal = $0 )
2023	2022	BRIGHAM YOUNG UNIVERSITY	A-153 ASB	PROVO	UT	84602	UTAH	USA	Trans-NIH Research Support	001	3	7/13/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2020	BRIGHAM YOUNG UNIVERSITY	A-153 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	3	7/12/2023	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $113,625 )
2022	2022	BRIGHAM YOUNG UNIVERSITY	A41 ASB	PROVO	UT	84602	UTAH	USA	Trans-NIH Research Support	001	3	8/10/2022	SUPPLEMENT FOR EXPANSION	$113,625
2022	2020	BRIGHAM YOUNG UNIVERSITY	A41 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	3	8/8/2022	COMPETING CONTINUATION	$0
														Subtotal = $113,625

Issue Date FY: 2020 ( Subtotal = $437,614 )
2020	2020	BRIGHAM YOUNG UNIVERSITY	A41 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	001	3	9/8/2020	COMPETING CONTINUATION	$437,614
2020	2016	BRIGHAM YOUNG UNIVERSITY	A41 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	2	7/8/2020	COMPETING CONTINUATION	$0
														Subtotal = $437,614

Issue Date FY: 2017 ( Subtotal = -$175 )
2017	2012	BRIGHAM YOUNG UNIVERSITY	A-41 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	1	9/30/2017	NEW	-$175
														Subtotal = -$175

Issue Date FY: 2016 ( Subtotal = $439,218 )
2016	2016	BRIGHAM YOUNG UNIVERSITY	D-177 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	002	2	3/24/2016	COMPETING CONTINUATION	$73,765
2016	2016	BRIGHAM YOUNG UNIVERSITY	D-177 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	001	2	1/12/2016	COMPETING CONTINUATION	$365,453
2016	2012	BRIGHAM YOUNG UNIVERSITY	D-177 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	1	1/7/2016	NEW	$0
														Subtotal = $439,218

Issue Date FY: 2012 ( Subtotal = $346,949 )
2012	2012	BRIGHAM YOUNG UNIVERSITY	D-177 ASB	PROVO	UT	84602	UTAH	USA	Biomedical Research and Research Training	000	1	2/27/2012	NEW	$346,949
														Subtotal = $346,949

Grand Total All Awards = $1,337,231

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the partitioning of glucose to lipids versus respiration, an undergraduate-based approach to dissect a pivotal point of metabolic control

Award Number: R15GM100376

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer