Tuesday, July 1, 2025 7/1/2025

Single-Cell Molecular Pathway Analysis in Aging Systems via Novel Mass Cytometry Methods

Award Number: R01AG084804
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Single-Cell Molecular Pathway Analysis in Aging Systems via Novel Mass Cytometry Methods - Summary Different cell types, each with unique composition, properties, and functions, are essential to sustain life in an organism. Bulk analysis of such heterogeneous mixtures of cells does not distinguish the characteristics of a given cell type or differences between cells within the same type, missing information that is key to understanding molecular mechanisms foundational to the rational design of therapies for disease and ailments. The goal of this proposal is to develop single-cell and imaging methods using metal-bearing probes to monitor metabolic processes in live cells such as siRNA delivery, protein synthesis, and post-translational modification. The cells will then be fixed and processed for subsequent detection of protein and mRNA markers. There are three aims: (1) Delivering molecular probes to viable cells to explore molecular pathways in single cells by CyTOF. (2) Barcoding prenylation probes to explore molecular pathways in mixed samples of single cells. (3) Exploring the effect of aging in murine primary cells by CyTOF and murine tissue by MIBI-ToF. The proposed work will expand the use of multi- parametric capabilities of mass cytometry (i.e. cytometry by time-of-flight, CyTOF, and multiplexed ion beam imaging by time-of-flight, MIBI-ToF) in the biotechnological and biomedical fields. The development of these methodologies will explore the causal relationship between autophagy and senescence in murine liver models, exploring the hypothesis that the mevalonate pathway provides a link between the two. The ultimate goal is to understand the relationship between autophagy, mevalonate, and senescence pathways in aging and inform emerging treatments to counteract the detrimental effects of senescent 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 = $384,294 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Aging Research	000	2	4/18/2025	NON-COMPETING CONTINUATION	$352,922
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Aging Research	001	2	6/20/2025	NON-COMPETING CONTINUATION	$31,372
														Subtotal = $384,294

Issue Date FY: 2024 ( Subtotal = $490,776 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Aging Research	000	1	5/30/2024	NEW	$490,776
														Subtotal = $490,776

Grand Total All Awards = $875,070

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Single-Cell Molecular Pathway Analysis in Aging Systems via Novel Mass Cytometry Methods

Award Number: R01AG084804

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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