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Discovery of disease-associated eQTLs with a scalable human in vitro model of microglia-astrocyte interactions

Award Number: R03AG091099
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2026
PERIOD OF PERFORMANCE END DATE: 03/14/2028

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Discovery of disease-associated eQTLs with a scalable human in vitro model of microglia-astrocyte interactions - PROJECT SUMMARY Dementias are projected to become the most burdening group of diseases, expected to affect over 150 million people worldwide by 2050, and Alzheimer’s disease (AD) is the most common among them. Currently, over 6 million Americans are living with AD. While there have been several recently-approved drugs for AD, these drugs target amyloid beta plaques – just one facet of the disease – and have not proven effective in all patients. Non-neuronal cell types in the brain such as microglia (the brain’s immune cells) and astrocytes (star- shaped helper cells) play a critical role in disease progression but have been traditionally understudied. Microglia are known to be activated by amyloid beta plaques and they were ascribed both a protective and a detrimental role. They were shown to induce a toxic state in astrocytes. The microglia’s behavior is likely influenced by patient genetics, which might explain why the majority of AD risk genes are expressed in microglia. To determine which of the 90 known AD-associated genetic variants exert their effect through microglia, we need a better understanding of the functional links between a variant and the disease. This requires large-scale studies of diseased, human cells from genetically diverse patients, as there is a wide variety of genetic variants that can influence AD risk. This project proposes to develop an automatable protocol for the creation of human induced pluripotent stem cell (iPSC)-derived microglia (iMG) and their co-culture with primary astrocytes. Standardized co-cultures of iMGs from AD patients and primary astrocytes will allow scientists to observe how these cells interact in a diseased environment, better understand known variants, and possibly identify new risk variants. Attaining sufficient statistical power for the identification of novel variants requires many cell lines, which can only be achieved with robotic automation. This study will serve as a proof of concept to demonstrate that such co-culture systems be automated and will later be scaled up to include additional cell lines. It will furthermore help to understand how certain genetic variants contribute to AD, which might inspire new therapeutic approaches.


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 = $354,000 )
2026	2026	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Aging Research	000	1	3/9/2026	NEW	$354,000
														Subtotal = $354,000

Grand Total All Awards = $354,000

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Discovery of disease-associated eQTLs with a scalable human in vitro model of microglia-astrocyte interactions

Award Number: R03AG091099

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2026

PERIOD OF PERFORMANCE END DATE: 03/14/2028

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