, Technology Core: This innovative integrated systems biology application seeks to delineate the complex host/pathogen interactions occurring at the alveolar level that lead to unsuccessful response to therapy in severe pneumonia. The overall goal of the Technology Core is to provide sample processing and data generation support for all projects and other cores in the Successful Clinical Response In Pneumonia Therapy (SCRIPT) Systems Biology Center. Our Technology Core is uniquely poised to contribute to the success of the SCRIPT Study, as we possess expertise in flow cytometry, cell sorting, various Next Generation Sequencing techniques, including RNA-seq for gene expression profiling and genome-wide bisulfite sequencing for genomic DNA methylation, and humanized mouse modeling. The Technology Core will process clinical samples, isolate specific cellular populations and perform their transcriptional and epigenetic profiling for Project 1 and the Data Management and Bioinformatics Core, and generate humanized MISTRG mice and perform transcriptional profiling of alveolar macrophages from these mice for Project 2 and the Modeling Core.
Aim 1 : To isolate and immunophenotype subsets of macrophages/monocytes and T cells from non- bronchoscopic bronchoalveolar lavage (NBBAL) and peripheral blood patients with pneumonia via fluorescence- activated cell sorting (FACS).
Aim 2 : To perform transcriptional and epigenetic profiling of macrophage and T cell subsets isolated from NBBAL from patients with pneumonia.
Aim 3 : To validate pathogen-specific gene expression signatures observed in patients with pneumonia using a humanized MISTRG mouse model.

Public Health Relevance

It is not required per instructions stated on the Funding Opportunity Announcement RFA-AI-16-080, Section IV. Application and Submission Information, Technology Core, Research & Related Other Project Information (Technology Core), ?Project Narrative: Do not complete?.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI135964-03
Application #
9843978
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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