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IDENTIFYING MICROBIAL MECHANISMS THAT REGULATE ANIMAL INSULIN SIGNALING

Award Number: DP2DK139569
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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IDENTIFYING MICROBIAL MECHANISMS THAT REGULATE ANIMAL INSULIN SIGNALING - PROJECT SUMMARY Insulin resistance and Type 2 diabetes affect nearly 10% of the population, and are on the rise. Recent evidence suggests that human intestinal bacteria can regulate insulin release, which implies that microorganisms harbor novel mechanisms or factors that influence insulin signaling. Identifying microorganisms and novel bacterial mechanisms of modulating animal insulin release in vivo is very challenging in mammals because of the extensive microbial diversity in the mammalian intestinal microbiota, and because resident microorganisms are resistant to colonization by artificially administered isolates. I have overcome these limitations by developing a novel, high-throughput C. elegans model for identifying bacterial isolates that regulate in vivo insulin signaling, and demonstrated (for the first time) that environmental bacteria contain previously undiscovered, novel mechanisms or factors for regulating animal insulin resistance. In this transformative project, I will perform the first-ever, large-scale screen for bioactive bacteria that modify animal insulin signaling; use transposon mutagenesis to identify those bacterial genes or factors responsible for regulating insulin signaling; and engineer at least one human probiotic strain to express a bacterial insulin-regulating system or factor. Taken together, this project will generate new insights into the types of bacteria that modify animal insulin signaling; the mechanisms bacteria have evolved to do so; and provide the field with fundamentally new directions and strategies for alleviating one of the most common and impactful human pathologies in existence.


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 = $1,140,000 )
2026	2026	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/12/2026	EXTENSION WITH OR WITHOUT FUNDS	$1,140,000
														Subtotal = $1,140,000

Issue Date FY: 2023 ( Subtotal = $1,710,000 )
2023	2023	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/15/2023	NEW	$1,710,000
														Subtotal = $1,710,000

Grand Total All Awards = $2,850,000

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IDENTIFYING MICROBIAL MECHANISMS THAT REGULATE ANIMAL INSULIN SIGNALING

Award Number: DP2DK139569

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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