With support from the NCRR COBRE Program Project and the Cystic Fibrosis Foundation Research Development Program, the Lung Biology Center offers a Host-Pathogen Interactions Core:
The goals of the Host-Pathogen Interaction Core are to:
1) Facilitate research on biological mechanisms that contribute to lung disease. The infrastructure and expertise of the Core supports basic science studies, including protein localization and trafficking, gene regulation and microbial co-culture experiments.
2) Accelerate therapeutic development. The Core allows investigators to build on basic studies to facilitate drug discovery and preclinical investigations, thereby directly enhancing the translational impact of COBRE-affiliated groups. The Core also provides expertise to biotechnology and pharmaceutical companies developing new therapies to treat lung disease.
This model is used to study the impact of bacterial biofilms on CF-derived airway cells. Originally developed with a single species biofilm of Pseudomonas aeruginosa, the core has recently expanded this model to include polymicrobial biofilms that more accurately represent the microbial communities in the airway. The composition of these communities reflect findings of the numerous microbiome studies supported by the Translational Research Core. The Dartmouth co-culture model has been used to dissect host-pathogen interactions, as well as serve as a platform to test new antimicrobial agents with efficacy versus these recalcitrant biofilm communities.
A focus of the core is to provide access to physiologically relevant cell lines for mechanistic studies, with a focus on polarized airway epithelial cells. The Core facility provides access to validated CF patient-derived bronchial epithelial (CFBE) cell lines, as well as primary patient airway cells through a collaborative arrangement with the University of North Carolina. Facilities and support are provided for the culture, maintenance, treatment and analysis of cells, including electrophysiological studies of transepithelial chloride efflux (Ussing chamber), as well as support for siRNA and transfection protocols. The Core also provides cellular and molecular reagents to both the Live Cell Imaging Core and Translational Research Cores.
This core assists researchers with screening and design of target inhibitors as well as preclinical testing and evaluation of new therapeutics aimed at diseases of the lung, including targeting the chronic infections associated with Cystic Fibrosis.These resources are available to in-house research projects, as well as on a contract basis for pharmaceutical and biotechnology collaborators working on therapeutics relevant to the lung.
The Core also fulfills a critical function as a “water-cooler”, ensuring that as new state-of-the-art techniques in lung biology research are adopted by individual scientists or groups, they are rapidly distributed to the other members of the program. It also provides hands-on training for graduate students and post-doctoral fellows in the COBRE laboratories, and will also sponsor trainee participation in extramural workshops (e.g. Cold Spring Harbor, MBL). In addition, the Core partners with affiliated Departments to invite outside speakers with expertise, particularly in trafficking and drug-discovery.