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Multilineage DAmFRET to investigate AD/ADRD protein phase behavior in neural tissue models

Award Number: R21AG080434
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Multilineage DAmFRET to investigate AD/ADRD protein phase behavior in neural tissue models - Project Summary/Abstract Alzheimer's Disease and Related Dementias (AD/ADRD) are the most common forms of dementia. No treatments exist to stop or prevent them. AD/ADRD are caused in part by the aggregation of one, or more often a combination of, specific proteins. TDP-43 is one of a handful of such proteins. It characteristically transitions from a dynamic liquid phase of assembly to a rigid and pathogenic phase in a large fraction of dementia cases. This transition occurs against a backdrop of progressive changes in the interactions between different cell types in the brain. An interdependence of these molecular and cellular changes likely determines the clinical courses of AD/ADRD, but to understand that interdependence, we need new tools with which to compare protein phase transitions and their corresponding phenotype effects in the context of interacting brain cell types. We propose here to develop such a tool by modifying a cell-based biophysical method, Distributed Amphifluoric FRET (DAmFRET) for use in human induced pluripotent stem cell (hiPSC)-derived brain tissue models (Aim 1). We will simultaneously use DAmFRET to develop TDP-43 as a reporter of cell type-specific differences in the homeostasis of protein phase transitions (Aim 2). By completing these aims, we will have created and validated a uniquely powerful tool for better understanding the complex molecular and cellular causes of AD/ADRD.


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 = $0 )
2026	2024	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Aging Research	000	2	6/2/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $206,250 )
2024	2024	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Aging Research	000	2	1/9/2024	NON-COMPETING CONTINUATION	$185,625
2024	2024	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Aging Research	001	2	6/11/2024	NON-COMPETING CONTINUATION	$20,625
														Subtotal = $206,250

Issue Date FY: 2023 ( Subtotal = $206,250 )
2023	2023	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Aging Research	000	1	1/25/2023	NEW	$206,250
														Subtotal = $206,250

Grand Total All Awards = $412,500

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Multilineage DAmFRET to investigate AD/ADRD protein phase behavior in neural tissue models

Award Number: R21AG080434

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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