Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Integration of mononuclear phagocytes into the human gastrointestinal GOFlowChip for investigation of luminal antigen sampling

Award Number: U01EB029242
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2025

Group Awards By:

View Award Description

Integration of mononuclear phagocytes into the human gastrointestinal GOFlowChip for investigation of luminal antigen sampling - PROJECT SUMMARY This project will develop novel in vitro models of the human gastrointestinal (GI) tract for understanding natural cellular responses to microbes and the induction of immune tolerance and activation. The development of gastrointestinal organoids, 3-D permanent cultures of complex primary epithelial cell populations embedded in an extracellular matrix, has revolutionized research in gastrointestinal development, microbiology and immunology in the past 5 years. For our project, we have assembled a trans-disciplinary team of investigators with expertise in bioengineering (Wilking, Chang), immunology (Bimczok, Jutila), and human microbiome research (Walk) to significantly advance 3-D gut organoid-microbiome co-culture systems. Our team has recently established a millifluidic gut-on-a chip-platform, the GoFlowChip, that recapitulates luminal and basal flow in human intestinal organoids. In parallel investigations, we have established co-cultures of primary human monocyte-derived DCs and human gastric spheroids that we have successfully infected with H. pylori. Here, we seek to leverage the unique capabilities of our two models and combine them into a single analytical platform to study antigen sampling from the gastrointestinal lumen for the induction of adaptive mucosal immunity or tolerance. Specifically, we seek to define and quantify the contributions of candidate mechanisms including transepithelial dendrite formation and Fc-receptor-dependent transcytosis that enable mononuclear phagocytes (MNPs) to acquire luminal antigens. We hypothesize that distinct mechanisms of MNP antigen acquisition are reproduced and can be quantitatively analyzed using the GOFlowChip platform and that colonizing bacteria and fluid dynamics regulate epithelial antigen transport. To test our hypotheses, we will (1) Develop and validate a chip-based organoid-DC co-culture system with luminal and basolateral flow capacity. (2) Quantify the net effect of biologic complexity on GI organoid biology and MNP interaction. (3) Elucidate the mechanisms involved in bacterial antigen sampling from the gastrointestinal lumen by human MNPs. This approach will enable us to optimize our integrated GoFlowChip co-culture system as a powerful new tool for the field for studies on vaccine or drug delivery and on the impact of intestinal microbiota on antigen sampling. The proposed research is conceptually innovative, because it integrates all three necessary cell types (epithelial, microbial, and immune) involved in mucosal host-microbe interactions. The GoFlowChip platform is technologically innovative, because it replicates a complex, oxygen-utilizing epithelium and a microbially colonized lumen, is the first to incorporate fluidics into 3-D organoid cultures, and reproduces the intimate interactions that naturally occur between the gastrointestinal epithelium and sentinel MNPs. The proposed research is significant, because it will provide an incredibly powerful new tool to address fundamental, mechanistic questions in human mucosal biology, microbiology, and immunology in the context of human health and disease.


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 = -$39,447 )
2026	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	6/4/2026	NON-COMPETING CONTINUATION	-$39,447
														Subtotal = -$39,447

Issue Date FY: 2024 ( Subtotal = -$3,620 )
2024	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	9/11/2024	SUPPLEMENT FOR EXPANSION	-$3,620
														Subtotal = -$3,620

Issue Date FY: 2023 ( Subtotal = $611,538 )
2023	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	8/2/2023	NON-COMPETING CONTINUATION	$611,538
														Subtotal = $611,538

Issue Date FY: 2022 ( Subtotal = $611,538 )
2022	2022	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	9/1/2022	NON-COMPETING CONTINUATION	$611,538
2022	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	9/16/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	1/28/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $611,538

Issue Date FY: 2021 ( Subtotal = $1,140,707 )
2021	2021	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	3/23/2021	SUPPLEMENT FOR EXPANSION	$79,051
2021	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	3	8/3/2021	NON-COMPETING CONTINUATION	$599,308
2021	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	2	6/2/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	005	3	8/16/2021	SUPPLEMENT FOR EXPANSION	$462,348
2021	2020	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	2/17/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	3/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,140,707

Issue Date FY: 2020 ( Subtotal = $1,105,333 )
2020	2020	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	9/22/2020	SUPPLEMENT FOR EXPANSION	$493,788
2020	2020	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	9/14/2020	NON-COMPETING CONTINUATION	$611,545
														Subtotal = $1,105,333

Issue Date FY: 2019 ( Subtotal = $565,366 )
2019	2019	MONTANA STATE UNIVERSITY, INC	307 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/17/2019	NEW	$565,366
														Subtotal = $565,366

Grand Total All Awards = $3,991,415

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Integration of mononuclear phagocytes into the human gastrointestinal GOFlowChip for investigation of luminal antigen sampling

Award Number: U01EB029242

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer