Simon L. Dove

Department of Pediatrics
Department of Microbiology and Molecular Genetics
Children's Hospital
Division of Infectious Diseases
Enders Building, Room 754
300 Longwood Ave.
Boston, MA 02115
Tel: (617) 919-2888
Fax: (617) 730-0254
Email: simon.dove@childrens.harvard.edu
3 postdoctoral fellows, 3 graduate students

Successful infection of a host organism by a bacterial pathogen depends critically on its ability to make the appropriate virulence factors at the right time and place. This is achieved through the coordinate regulation of virulence genes, the expression of which is typically controlled at the level of transcription by proteins that modulate the activity of RNA polymerase (RNAP). Research in my laboratory focuses on the regulation of transcription in pathogenic bacteria with emphasis on regulators that contact RNAP, and regulators that control virulence gene expression.

Several current projects concern the regulation of virulence gene expression in Pseudomonas aeruginosa, a pathogen that infects the lungs of cystic fibrosis (CF) patients. In the chronically infected CF lung the organism persists as a biofilm—a surface attached community of bacteria encased in a polymeric matrix. Prominent amongst those genes that play a role in biofilm formation in P. aeruginosa are the cupA genes, which encode components of a putative fimbrial structure that facilitates surface-attachment. We have found that MvaT, a member of the H-NS family of proteins, controls the phase-variable (i.e. ON/OFF) expression of the cupA fimbrial gene cluster. Current work is aimed at determining how MvaT exerts this control.

Other work in the laboratory involves the study of two related transcription regulators from the intracellular pathogen Francisella tularensis, the causative agent of tularemia. These two regulators form a complex that associates with RNAP to positively control virulence gene expression in this organism. We are interested in determining how these regulators, which do not appear to bind DNA, influence the expression of specific target genes.

References:

Charity, J.C., Blalock, L.T., Costante-Hamm, M.M., Kasper, D.L., and Dove, S.L. (2009) Small molecule control of virulence gene expression in Francisella tularensis. PLoS Pathog. 5, e1000641.
Turner, K.H., Vallet-Gely, I., and Dove, S.L. (2009) Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a LysR-type transcription regulator. PLoS Genet. 5, e1000779.
Castang, S., McManus, H.R., Turner, K.H., and Dove, S.L. (2008) H-NS family members function coordinately in an opportunistic pathogen. Proc. Natl. Acad. Sci. USA. 105, 18947-18952.
Vallet-Gely, I., Sharp, J.S., and Dove, S.L. (2007) Local and global regulators linking anaerobiosis to cupA fimbrial gene expression in Pseudomonas aeruginosa. J. Bacteriol. 189, 8667-8676.

BBS webpage updated 5/15/2010