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Multi-omics approach to understanding the beneficial effects of exercise in diabetes

Award Number: F32DK126432
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Multi-omics approach to understanding the beneficial effects of exercise in diabetes - PROJECT SUMMARY Determining the molecular mechanisms mediating the health benefits of exercise is a challenging, but extremely important undertaking, that can lead to the identification of novel therapeutic targets. The significance of this area of research is underscored by the large-scale NIH initiative “Molecular Transducers of Physical Activity Consortium” (MoTrPAC), which aims to understand the molecular footprint of exercise in healthy humans and rats. While the extensive, in-depth data provided by MoTrPAC will be a landmark project, this consortium will only study healthy humans and rodents. Thus, the molecular footprint of exercise under conditions of obesity and other metabolic diseases may remain largely unknown, even in the post-MoTrPAC era. The overall goal of this project is to use state-of-the art omics platforms to discover the mechanism by which exercise training improves health under conditions of metabolic disease. Specific Aims are to determine: a) tissue-specific changes in cell types and cell composition in response to exercise and diet; b) tissue-specific transcriptional responses and activation of molecular pathways that can reverse the unfavorable metabolic effects of diet- induced obesity; and c) cell-type and tissue crosstalk in both lean and obese mice. Analysis of these complex data using computational biology tools has the power to unravel the molecular basis of disease and identify therapeutic targets. This large-scale project has two phases. The first phase includes the collection of multiple tissues from insulin resistant mice treated with or without exercise and second phase is multi-omics and bioinformatics analysis of these samples. The first phase of this project has recently been completed by the applicant, allowing for a feasible 2-year research plan to complete the second phase of the project. For the first phase, mice were divided in four groups: sedentary chow-fed; trained chow-fed; sedentary high fat diet-fed; and trained high fat diet-fed. Diet treatments were for 6 weeks and exercise training was done by housing mice with free access to a running wheel for 3 weeks. Seven tissues known to play significant roles in metabolism were collected: triceps, subcutaneous and visceral white adipose tissue, small intestine, hypothalamus, hippocampus and brain cortex. Phase 2 of this project is to perform single-cell transcriptomics and metabolomics on all collected tissues followed by data analysis and integration using computational biology tools. The applicant’s training plan will include dedicated mentorship by both Dr. Laurie Goodyear (sponsor) in the areas of exercise, metabolism, and diabetes, and Dr. Manolis Kellis (co-sponsor) for multi-omic approaches and computational biology. The applicant will also complete formal bioinformatics training through Harvard and MIT. These activities will provide her with the necessary tools critical for development as an independent physician scientist. This project will not only provide an outstanding training opportunity for the applicant, but should also lead to discoveries with broad implications for the treatment of obesity 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: 2025 ( Subtotal = $0 )
2025	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/24/2023	NON-COMPETING CONTINUATION	$0
2023	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	7/24/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $146,961 )
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/10/2021	NON-COMPETING CONTINUATION	$81,642
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/20/2021	NON-COMPETING CONTINUATION	$0
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	2	9/8/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	9/8/2021	NON-COMPETING CONTINUATION	$0
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	8/20/2021	SUPPLEMENT FOR EXPANSION	$65,319
														Subtotal = $146,961

Issue Date FY: 2020 ( Subtotal = $80,358 )
2020	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/11/2020	NEW	$80,358
2020	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/11/2020	NEW	$0
														Subtotal = $80,358

Grand Total All Awards = $227,319

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Multi-omics approach to understanding the beneficial effects of exercise in diabetes

Award Number: F32DK126432

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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