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

> **NIH NIH U01** · MONTANA STATE UNIVERSITY - BOZEMAN · 2021 · $79,051

## Abstract

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 ...

## Key facts

- **NIH application ID:** 10286736
- **Project number:** 3U01EB029242-02S2
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** Diane Bimczok
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,051
- **Award type:** 3
- **Project period:** 2021-03-24 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286736

## Citation

> US National Institutes of Health, RePORTER application 10286736, Integration of mononuclear phagocytes into the human gastrointestinal GOFlowChip for investigation of luminal antigen sampling (3U01EB029242-02S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10286736. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*