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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI142733-03
Application #
10113531
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2019-03-05
Project End
2024-02-29
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609