# Development of 3D Alveolar Tissue Models, CRISPR-editing and Microbiota-immune Response Assay Platforms for Deciphering Human Lung Immunity

> **NIH NIH U19** · JACKSON LABORATORY · 2022 · $419,002

## Abstract

PROJECT SUMMARY TECHNOLOGY DEVELOPMENT PROJECT
The goal of the Technology Development project (Tech Dev) is to develop approaches, tools and assays that
address the needs of The Jackson Laboratory Cooperative Center on Human Immunology (JAX CCHI) and that
advance the capabilities of the scientific community to tackle questions regarding human lung immunity, human
immune-microbiota interactions and basic mechanisms of immune cells. Major questions related to lung immune
function remain unanswered—such as the cell-to-cell interactions between immune and lung epithelial cells that
shape responses to foreign agents, or how the presence of microbiota in the airways or within lung compartments
influences the pathogenesis of viral infections and other lung diseases. A significant technical barrier to studying
human immune-lung dynamics is the sheer complexity of the human lung—which constantly filters airborne
particles, infectious organisms and air through dynamic interactions between the lung epithelium and resident
immune cells such as macrophages or dendritic cells. This complexity cannot be easily modeled in animal
systems or using deceased human lung tissue. To surmount these challenges, Tech Dev will focus on three
innovative human tissue platforms: 1) three-dimensional (3D) bioprinted models of the lung and upper respiratory
environment for investigating the functional lung-immune interactome during exposure to viral or metabolic
agents; 2) CRISPR/Cas9-based tools to genetically engineer primary human immune cell subsets, hematopoietic
stem cells and/or lung epithelial progenitors to probe cell function; and 3) a functional in vitro platform for
screening lung-resident microbiota and determining their impact on human lung immune responses. Each of
these platforms addresses a specific unmet need in the application and will enable us, respectively, to study the
human lung immunity within a dynamic and physiologically relevant microenvironment, to interrogate specific
cell types and molecular pathways predicted to respond to viral infections, and to assess the impact of bacterial
metabolites isolated from human airways on antiviral responses. Through these efforts, the JAX CCHI will be
equipped to address previously inaccessible questions related to lung-immune dynamics, towards a more
mechanistic understanding of lung immune function. Our Specific Aims are:
Aim 1. Develop in vitro models of human lung tissue-immune interactions using 3D bioprinting.
Aim 2: Optimize CRISPR-based genetic tools for use in engineering primary human immune and lung epithelial
cells.
Aim 3: Develop a functional immune assay platform to determine the immunomodulatory landscape of human
lung and airway microbiota.

## Key facts

- **NIH application ID:** 10371237
- **Project number:** 5U19AI142733-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Derya Unutmaz
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $419,002
- **Award type:** 5
- **Project period:** 2019-03-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371237

## Citation

> US National Institutes of Health, RePORTER application 10371237, Development of 3D Alveolar Tissue Models, CRISPR-editing and Microbiota-immune Response Assay Platforms for Deciphering Human Lung Immunity (5U19AI142733-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10371237. Licensed CC0.

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