The mission of the Host-Pathogen Interaction Core (HPIC) is to advance basic science, as well as translational and discovery studies relevant to lung disease. A central service of this Core is to provide expertise using a co-culture platform of bacterial biofilms on human airway cells developed at the Geisel School of Medicine at Dartmouth. This Core also provides a range of airway cell lines, as well as primary human airway epithelial cells from CF and non-CF donors, to support studies assessing host-pathogen interactions of relevance to the lung. This Core facilitates ongoing studies of COBRE Lung Biology Center (LBC) investigators and the pilot studies supported via this COBRE 111 application. The notable accomplishments of the HPIC include: 1) Development of a novel co-culture model system; 2) Assistance with a wide range of host-pathogen interaction studies by providing expertise in cell culture, siRNA and other molecular techniques, and electrophysiology studies; and 3) Coordinating with industry to develop new therapeutics aimed at chronic infections of the lung. The HPIC was launched in 2010 in response to a growing need by COBRE LBC investigators for support in crosscutting studies at the interface of bacterial pathogenesis and the host airway. We leveraged a set of earlier findings from the Stanton and O'Toole labs, in particular the study of bacterial biofilms on airway epithelial cells and host-pathogen interactions, to build a critical set of novel capabilities that have been used extensively by LBC investigators since the inception of this core. The HPIC was developed to meet the unique research needs of LBC investigators and received approval and strong backing from the External Advisory Committee, who deemed it critical to meet the needs of the evolving LBC. This Core is directed by George OToole, Ph.D., Professor of Microbiology and Immunology. Dr. OToole has over 20 years of experience in bacterial systems, and since 2000 has worked closely with Dr. Bruce Stanton, COBRE Director and PI, on a variety of projects that directly resulted in the development of the central capabilities of this Core.

Public Health Relevance

Infectious respiratory diseases are the third leading cause of death in the U.S. The studies described in this application will lead to a better understanding of how opportunistic pathogens, including Pseudomonas aeruginosa, cause chronic respiratory infections, and to new drugs / therapies to treat infectious respiratory disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Center Core Grants (P30)
Project #
4P30GM106394-04
Application #
9115190
Study Section
Special Emphasis Panel (ZGM1-TWD-C)
Project Start
Project End
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
4
Fiscal Year
2016
Total Cost
$147,851
Indirect Cost
$56,585
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Facciponte, Dominic N; Bough, Matthew W; Seidler, Darius et al. (2018) Identifying aerosolized cyanobacteria in the human respiratory tract: A proposed mechanism for cyanotoxin-associated diseases. Sci Total Environ 645:1003-1013
Grahl, Nora; Dolben, Emily L; Filkins, Laura M et al. (2018) Profiling of Bacterial and Fungal Microbial Communities in Cystic Fibrosis Sputum Using RNA. mSphere 3:
Hvorecny, Kelli L; Dolben, Emily; Moreau-Marquis, Sophie et al. (2018) An epoxide hydrolase secreted by Pseudomonas aeruginosa decreases mucociliary transport and hinders bacterial clearance from the lung. Am J Physiol Lung Cell Mol Physiol 314:L150-L156
Torres, Iviana M; Patankar, Yash R; Berwin, Brent (2018) Acidosis exacerbates in vivo IL-1-dependent inflammatory responses and neutrophil recruitment during pulmonary Pseudomonas aeruginosa infection. Am J Physiol Lung Cell Mol Physiol 314:L225-L235
Dhingra, Sourabh; Buckey, Jay C; Cramer, Robert A (2018) Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes. Antimicrob Agents Chemother 62:
Ries, Laure Nicolas Annick; Beattie, Sarah; Cramer, Robert A et al. (2018) Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi. Mol Microbiol 107:277-297
Nair, Dhanalakshmi R; Chen, Ji; Monteiro, João M et al. (2017) A quinolinol-based small molecule with anti-MRSA activity that targets bacterial membrane and promotes fermentative metabolism. J Antibiot (Tokyo) 70:1009-1019
Shlezinger, Neta; Irmer, Henriette; Dhingra, Sourabh et al. (2017) Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death. Science 357:1037-1041
Thammahong, Arsa; Caffrey-Card, Alayna K; Dhingra, Sourabh et al. (2017) Aspergillus fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis through Modulation of Chitin Synthase Activity. MBio 8:
Demirdjian, Sally; Schutz, Kristin; Wargo, Matthew J et al. (2017) The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and non-motile Pseudomonas aeruginosa. Mol Immunol 92:106-115

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