Project 1: Regulation Of Biofilm Development On Epithelial Cells And Abiotic Surfaces By Pseudomonas Aeruginosa

George O’Toole, Ph.D.

George O’Toole, Ph.D., is an Assistant Professor in the Department of Microbiology at Dartmouth Medical School. The focus of his research is to study the virulence mechanisms of the respiratory pathogen P. aeruginosa. In his COBRE project, he proposes that there are distinct regulatory pathways that control the transition between planktonic and biofilm growth of P. aeruginosa, and that these regulatory pathways are controlled in response to regulatory signals. He has identified a 3-component regulatory system (designated SadARS) comprised of a sensor histidine kinase and two associated response regulators that are required for biofilm development. The SadARS system is similar to the Bvg virulence gene regulatory locus of Bordetella pertussis both in terms of DNA sequence and genomic organization. In preliminary studies he has demonstrated that the SadARS locus is required for the maturation of biofilms on abiotic surfaces. Strains lacking a functional SadARS locus also show altered colonization of airway-derived human respiratory epithelial cells isolated from CF patients. The specific aims of this proposal are to: (1) Identify and functionally characterize the targets of the SadARS 3-component regulatory system; (2) Investigate the role of electron transport system (ETS) signaling via the SadARS system in biofilm development, and (3) Determine the small molecule(s) and receptor determinant(s) required to signal via the periplasmic domain of the SadS sensor histidine kinase. These experiments should provide novel insight into a regulatory cascade required for biofilm development, especially as it pertains to colonization of airway-derived epithelial cells in both CF and non-CF individuals. Information from these studies may lead to identification of new targets for anti-biofilm therapies to treat respiratory infections.

Dr. O’Toole has collaborative, ongoing studies with other COBRE investigators including Drs. Swiatecka-Urban (Project 2), Madden (Project 3), and Stanton and he describes potential new collaborations with Drs. Treadwell (Project 4), Duell and Shi (Project 5), in his research proposal. Furthermore, Dr. O’Toole will be one of the major users of the COBRE Proteomics Core.

Dr. O’Toole’s mentor is Ronald Taylor, Ph.D., Professor of Microbiology and Immunology.

To learn more about research in the O'Toole Lab please visit the O'Toole Lab Home Page.