Infection and Immunity

 

Cluster_Pseudocolor(P. aeruginosa cluster (green rods) and S. aureus (red spheres))

Respiratory failure due to chronic infections and aberrant inflammatory responses, is the primary cause of death in patients with Cystic Fibrosis (CF). The significant expansion of infection and immunity related research in our CF Center prompted the establishment of a new core, the Infection and Immunity (I&I) Core.The collective expertise of the I&I Core Directors and Associate Directors sets the stage for innovative studies to examine defects in host response and microbial adaptation during CF, as well as testing new therapeutic approaches to tackle the destructive and life-threatening infections and inappropriate immune responses that play a major role in CF pathophysiology.

Goal: Provide experimental expertise, reagents and consultation in experimentation and preliminary data generation pertaining to immunology or microbiology projects in CF research

Our five objectives:

Develop models to study host-pathogen interactions and bacterial biofilm growth in CF
To support the CF Investigators with expertise to examine host-pathogen interactions in CF, we have developed assays to examine the interaction and colonization of CF pathogens with the respiratory epithelium, utilizing primary human respiratory epithelial cells from Core A and organotypic cultures, as well as CF clinical isolates of bacteria from Core D.

Provide immunological assays to assess dysfunction in CF
This core component will provide a comprehensive suite of immunologic assays to assess immune defects in CF, including multi-plex assays using the BioRad MagPix platform (which allows up to 50 cytokines to be analyzed at the same time), classical cytokine detection and quantification, flow cytometry, and enzymatic assays to assess immune cell function.

Provide animal models of lung infection, including epithelial-specific knockout models
Mouse models of acute and chronic infections with a variety of CF pathogens (bacterial, viral and fungal) have been developed, as well as polymicrobial infection models, histological assessments of lung injury and physiologic measurements, using the forced-oscillation technique.

Provide support and expertise for next-generation sequencing assays
To explore novel pathways involved in CF pathogenesis, the I&I Core will provide state-of-the-art next-gen sequencing methods including 16S sequencing, total RNA-seq, Dual-seq, ATAC-seq, single-cell RNA-seq and IgSeq. Utilizing these methods will set our CF Investigators on pace to tackle pioneering microbiology and immunology questions

Provide bioinformatics support
A crucial component to providing access to the latest next-gen sequencing technologies is bioinformatics and biostatistics consultation and analytical support, as well as expertise in predictive modeling, which will allow our teams to integrate sequencing data with patient metadata to identify new targets for therapeutic intervention to improve the disease course for CF patients.