ABOUT THE RESEARCHER

OVERVIEW

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 could 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.

BACKGROUND

Simon Dove received his PhD from the University of Dundee in the UK and undertook Postdoctoral training in the Department of Microbiology and Molecular Genetics at Harvard Medical School.

Selected Publications

  1.  Goldman, S.R., Sharp, J.S., Vvedenskaya, I.O., Livny, J., Dove, S.L., and Nickels, B.E. (2011) NanoRNAs prime transcription initiation in vivo. Mol. Cell 42, 817-825.
  2. Castang, S., and Dove, S.L. (2010) High-order oligomerization is required for the function of the H-NS family member MvaT in Pseudomonas aeruginosaMol. Microbiol. 78, 916-931.
  3. 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.
  4. 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.