BBS Faculty Member - Simon Dove

Simon Dove

Department of Pediatrics
Department of Microbiology and Immunobiology

Boston Children's Hospital
Infectious Dis., Enders Bldg., Room 761.1
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2888
Fax: 617-730-0254
Email: simon.dove@childrens.harvard.edu
Lab Members: 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.

We have begun to investigate the role that small 2-4 nucleotide RNA transcripts, “nanoRNAs” play in the regulation of gene expression in bacteria. We have shown that nanoRNAs can prime transcription initiation in vivo and that when they do this results in large and widespread changes in gene expression. These findings establish that small RNA primers can be used to initiate transcription in vivo, challenging the conventional view that all cellular transcription occurs using only NTPs. Our findings further suggest that nanoRNAs represent a distinct class of functional small RNAs that can affect gene expression through direct incorporation into a target RNA transcript rather than through a traditional antisense-based mechanism.



Last Update: 1/13/2014



Publications

For a complete listing of publications click here.

 


 

Castang, S., and Dove, S.L. (2012) Basis for the essentiality of H-NS family members in Pseudomonas aeruginosa. J. Bacteriol. (In press.)

Vvedenskaya, I.O., Sharp, J.S., Goldman, S.R., Kanabar, P.N., Livny, J., Dove, S.L., and Nickels, B.E. (2012) Growth-phase-dependent control of transcription start site selection and gene expression by nanoRNAs.
Genes Dev. 26, 1498-1507.

McManus, H.R., and Dove, S.L. (2011) The CgrA and CgrC proteins form a complex that positively regulates
cupA fimbrial gene expression in Pseudomonas aeruginosa. J. Bacteriol. 193, 6152-6161.

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.



© 2013 by the President and Fellows of Harvard College