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.


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.


Publications powered by Harvard Catalyst Profiles

  1. Ramsey KM, Ledvina HE, Tresko TM, Wandzilak JM, Tower CA, Tallo T, Schramm CE, Peterson SB, Skerrett SJ, Mougous JD, Dove SL. Tn-Seq reveals hidden complexity in the utilization of host-derived glutathione in Francisella tularensis. PLoS Pathog. 2020 Jun; 16(6):e1008566. View abstract
  2. Gebhardt MJ, Kambara TK, Ramsey KM, Dove SL. Widespread targeting of nascent transcripts by RsmA in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2020 05 12; 117(19):10520-10529. View abstract
  3. Sharp JS, Rietsch A, Dove SL. RNase E Promotes Expression of Type III Secretion System Genes in Pseudomonas aeruginosa. J Bacteriol. 2019 11 15; 201(22). View abstract
  4. Hill IT, Tallo T, Dorman MJ, Dove SL. Loss of RNA Chaperone Hfq Unveils a Toxic Pathway in Pseudomonas aeruginosa. J Bacteriol. 2019 10 15; 201(20). View abstract
  5. Lynskey NN, Velarde JJ, Finn MB, Dove SL, Wessels MR. RocA Binds CsrS To Modulate CsrRS-Mediated Gene Regulation in Group A Streptococcus. mBio. 2019 07 16; 10(4). View abstract
  6. Kambara TK, Ramsey KM, Dove SL. Pervasive Targeting of Nascent Transcripts by Hfq. Cell Rep. 2018 05 01; 23(5):1543-1552. View abstract
  7. Rohlfing AE, Ramsey KM, Dove SL. Polyphosphate Kinase Antagonizes Virulence Gene Expression in Francisella tularensis. J Bacteriol. 2018 02 01; 200(3). View abstract
  8. Cuthbert BJ, Ross W, Rohlfing AE, Dove SL, Gourse RL, Brennan RG, Schumacher MA. Dissection of the molecular circuitry controlling virulence in Francisella tularensis. Genes Dev. 2017 08 01; 31(15):1549-1560. View abstract
  9. Basset A, Herd M, Daly R, Dove SL, Malley R. The Pneumococcal Type 1 Pilus Genes Are Thermoregulated and Are Repressed by a Member of the Snf2 Protein Family. J Bacteriol. 2017 08 01; 199(15). View abstract
  10. Eshraghi A, Kim J, Walls AC, Ledvina HE, Miller CN, Ramsey KM, Whitney JC, Radey MC, Peterson SB, Ruhland BR, Tran BQ, Goo YA, Goodlett DR, Dove SL, Celli J, Veesler D, Mougous JD. Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth. Cell Host Microbe. 2016 Nov 09; 20(5):573-583. View abstract
  11. Ramsey KM, Dove SL. A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti-virulence factor. Mol Microbiol. 2016 08; 101(4):688-700. View abstract
  12. McGuffie BA, Vallet-Gely I, Dove SL. s Factor and Anti-s Factor That Control Swarming Motility and Biofilm Formation in Pseudomonas aeruginosa. J Bacteriol. 2015 Nov 30; 198(5):755-65. View abstract
  13. Druzhinin SY, Tran NT, Skalenko KS, Goldman SR, Knoblauch JG, Dove SL, Nickels BE. A Conserved Pattern of Primer-Dependent Transcription Initiation in Escherichia coli and Vibrio cholerae Revealed by 5' RNA-seq. PLoS Genet. 2015 Jul; 11(7):e1005348. View abstract
  14. McFarland KA, Dolben EL, LeRoux M, Kambara TK, Ramsey KM, Kirkpatrick RL, Mougous JD, Hogan DA, Dove SL. A self-lysis pathway that enhances the virulence of a pathogenic bacterium. Proc Natl Acad Sci U S A. 2015 Jul 07; 112(27):8433-8. View abstract
  15. Ding P, McFarland KA, Jin S, Tong G, Duan B, Yang A, Hughes TR, Liu J, Dove SL, Navarre WW, Xia B. A Novel AT-Rich DNA Recognition Mechanism for Bacterial Xenogeneic Silencer MvaT. PLoS Pathog. 2015 Jun; 11(6):e1004967. View abstract
  16. Ramsey KM, Osborne ML, Vvedenskaya IO, Su C, Nickels BE, Dove SL. Ubiquitous promoter-localization of essential virulence regulators in Francisella tularensis. PLoS Pathog. 2015 Apr; 11(4):e1004793. View abstract
  17. Winardhi RS, Castang S, Dove SL, Yan J. Single-molecule study on histone-like nucleoid-structuring protein (H-NS) paralogue in Pseudomonas aeruginosa: MvaU bears DNA organization mode similarities to MvaT. PLoS One. 2014; 9(11):e112246. View abstract
  18. Rohlfing AE, Dove SL. Coordinate control of virulence gene expression in Francisella tularensis involves direct interaction between key regulators. J Bacteriol. 2014 Oct; 196(19):3516-26. View abstract
  19. Balasubramanian D, Kumari H, Jaric M, Fernandez M, Turner KH, Dove SL, Narasimhan G, Lory S, Mathee K. Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response. Nucleic Acids Res. 2014 Jan; 42(2):979-98. View abstract
  20. Jackson AA, Gross MJ, Daniels EF, Hampton TH, Hammond JH, Vallet-Gely I, Dove SL, Stanton BA, Hogan DA. Anr and its activation by PlcH activity in Pseudomonas aeruginosa host colonization and virulence. J Bacteriol. 2013 Jul; 195(13):3093-104. View abstract
  21. Castang S, Dove SL. Basis for the essentiality of H-NS family members in Pseudomonas aeruginosa. J Bacteriol. 2012 Sep; 194(18):5101-9. View abstract
  22. Winardhi RS, Fu W, Castang S, Li Y, Dove SL, Yan J. Higher order oligomerization is required for H-NS family member MvaT to form gene-silencing nucleoprotein filament. Nucleic Acids Res. 2012 Oct; 40(18):8942-52. View abstract
  23. Vvedenskaya IO, Sharp JS, Goldman SR, Kanabar PN, Livny J, Dove SL, Nickels BE. Growth phase-dependent control of transcription start site selection and gene expression by nanoRNAs. Genes Dev. 2012 Jul 01; 26(13):1498-507. View abstract
  24. Li M, Le Trong I, Carl MA, Larson ET, Chou S, De Leon JA, Dove SL, Stenkamp RE, Mougous JD. Structural basis for type VI secretion effector recognition by a cognate immunity protein. PLoS Pathog. 2012; 8(4):e1002613. View abstract
  25. Basset A, Turner KH, Boush E, Sayeed S, Dove SL, Malley R. An epigenetic switch mediates bistable expression of the type 1 pilus genes in Streptococcus pneumoniae. J Bacteriol. 2012 Mar; 194(5):1088-91. View abstract
  26. McManus HR, Dove SL. The CgrA and CgrC proteins form a complex that positively regulates cupA fimbrial gene expression in Pseudomonas aeruginosa. J Bacteriol. 2011 Nov; 193(22):6152-61. View abstract
  27. Goldman SR, Sharp JS, Vvedenskaya IO, Livny J, Dove SL, Nickels BE. NanoRNAs prime transcription initiation in vivo. Mol Cell. 2011 Jun 24; 42(6):817-25. View abstract
  28. Nickels BE, Dove SL. NanoRNAs: a class of small RNAs that can prime transcription initiation in bacteria. J Mol Biol. 2011 Oct 07; 412(5):772-81. View abstract
  29. Basset A, Turner KH, Boush E, Sayeed S, Dove SL, Malley R. Expression of the type 1 pneumococcal pilus is bistable and negatively regulated by the structural component RrgA. Infect Immun. 2011 Aug; 79(8):2974-83. View abstract
  30. Cho H, McManus HR, Dove SL, Bernhardt TG. Nucleoid occlusion factor SlmA is a DNA-activated FtsZ polymerization antagonist. Proc Natl Acad Sci U S A. 2011 Mar 01; 108(9):3773-8. View abstract
  31. Karna SL, Zogaj X, Barker JR, Seshu J, Dove SL, Klose KE. A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening of protein-protein interactions. Biotechniques. 2010 Nov; 49(5):831-3. View abstract
  32. Castang S, Dove SL. High-order oligomerization is required for the function of the H-NS family member MvaT in Pseudomonas aeruginosa. Mol Microbiol. 2010 Nov; 78(4):916-31. View abstract
  33. Turner KH, Vallet-Gely I, Dove SL. Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a LysR-type transcription regulator. PLoS Genet. 2009 Dec; 5(12):e1000779. View abstract
  34. Charity JC, Blalock LT, Costante-Hamm MM, Kasper DL, Dove SL. Small molecule control of virulence gene expression in Francisella tularensis. PLoS Pathog. 2009 Oct; 5(10):e1000641. View abstract
  35. Brencic A, McFarland KA, McManus HR, Castang S, Mogno I, Dove SL, Lory S. The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs. Mol Microbiol. 2009 Aug; 73(3):434-45. View abstract
  36. Castang S, McManus HR, Turner KH, Dove SL. H-NS family members function coordinately in an opportunistic pathogen. Proc Natl Acad Sci U S A. 2008 Dec 02; 105(48):18947-52. View abstract
  37. Yuan AH, Gregory BD, Sharp JS, McCleary KD, Dove SL, Hochschild A. Rsd family proteins make simultaneous interactions with regions 2 and 4 of the primary sigma factor. Mol Microbiol. 2008 Dec; 70(5):1136-51. View abstract
  38. Johnson SJ, Close D, Robinson H, Vallet-Gely I, Dove SL, Hill CP. Crystal structure and RNA binding of the Tex protein from Pseudomonas aeruginosa. J Mol Biol. 2008 Apr 11; 377(5):1460-73. View abstract
  39. Vallet-Gely I, Sharp JS, Dove SL. Local and global regulators linking anaerobiosis to cupA fimbrial gene expression in Pseudomonas aeruginosa. J Bacteriol. 2007 Dec; 189(23):8667-76. View abstract
  40. Charity JC, Costante-Hamm MM, Balon EL, Boyd DH, Rubin EJ, Dove SL. Twin RNA polymerase-associated proteins control virulence gene expression in Francisella tularensis. PLoS Pathog. 2007 Jun; 3(6):e84. View abstract
  41. Vallet-Gely I, Donovan KE, Fang R, Joung JK, Dove SL. Repression of phase-variable cup gene expression by H-NS-like proteins in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2005 Aug 02; 102(31):11082-7. View abstract
  42. Rietsch A, Vallet-Gely I, Dove SL, Mekalanos JJ. ExsE, a secreted regulator of type III secretion genes in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2005 May 31; 102(22):8006-11. View abstract
  43. Sun L, Dove SL, Panaghie G, deHaseth PL, Hochschild A. An RNA polymerase mutant deficient in DNA melting facilitates study of activation mechanism: application to an artificial activator of transcription. J Mol Biol. 2004 Nov 05; 343(5):1171-82. View abstract
  44. Harnasch M, Grau S, Behrends C, Dove SL, Hochschild A, Iskandar MK, Xia W, Ehrmann M. Characterization of presenilin-amyloid precursor interaction using bacterial expression and two-hybrid systems for human membrane proteins. Mol Membr Biol. 2004 Nov-Dec; 21(6):373-83. View abstract
  45. Dove SL, Hochschild A. A bacterial two-hybrid system based on transcription activation. Methods Mol Biol. 2004; 261:231-46. View abstract
  46. Song T, Dove SL, Lee KH, Husson RN. RshA, an anti-sigma factor that regulates the activity of the mycobacterial stress response sigma factor SigH. Mol Microbiol. 2003 Nov; 50(3):949-59. View abstract
  47. Dove SL, Darst SA, Hochschild A. Region 4 of sigma as a target for transcription regulation. Mol Microbiol. 2003 May; 48(4):863-74. View abstract
  48. Dove SL. Studying protein-protein interactions using a bacterial two-hybrid system. Methods Mol Biol. 2003; 205:251-65. View abstract
  49. Nickels BE, Dove SL, Murakami KS, Darst SA, Hochschild A. Protein-protein and protein-DNA interactions of sigma70 region 4 involved in transcription activation by lambdacI. J Mol Biol. 2002 Nov 15; 324(1):17-34. View abstract
  50. Shaywitz AJ, Dove SL, Greenberg ME, Hochschild A. Analysis of phosphorylation-dependent protein-protein interactions using a bacterial two-hybrid system. Sci STKE. 2002 Jul 23; 2002(142):pl11. View abstract
  51. Pande S, Makela A, Dove SL, Nickels BE, Hochschild A, Hinton DM. The bacteriophage T4 transcription activator MotA interacts with the far-C-terminal region of the sigma70 subunit of Escherichia coli RNA polymerase. J Bacteriol. 2002 Jul; 184(14):3957-64. View abstract
  52. Kuznedelov K, Minakhin L, Niedziela-Majka A, Dove SL, Rogulja D, Nickels BE, Hochschild A, Heyduk T, Severinov K. A role for interaction of the RNA polymerase flap domain with the sigma subunit in promoter recognition. Science. 2002 Feb 01; 295(5556):855-7. View abstract
  53. Kelley MT, Bürckstümmer T, Wenzel-Seifert K, Dove S, Buschauer A, Seifert R. Distinct interaction of human and guinea pig histamine H2-receptor with guanidine-type agonists. Mol Pharmacol. 2001 Dec; 60(6):1210-25. View abstract
  54. Dove SL, Hochschild A. Bacterial two-hybrid analysis of interactions between region 4 of the sigma(70) subunit of RNA polymerase and the transcriptional regulators Rsd from Escherichia coli and AlgQ from Pseudomonas aeruginosa. J Bacteriol. 2001 Nov; 183(21):6413-21. View abstract
  55. Shaywitz AJ, Dove SL, Kornhauser JM, Hochschild A, Greenberg ME. Magnitude of the CREB-dependent transcriptional response is determined by the strength of the interaction between the kinase-inducible domain of CREB and the KIX domain of CREB-binding protein. Mol Cell Biol. 2000 Dec; 20(24):9409-22. View abstract
  56. Dove SL, Huang FW, Hochschild A. Mechanism for a transcriptional activator that works at the isomerization step. Proc Natl Acad Sci U S A. 2000 Nov 21; 97(24):13215-20. View abstract
  57. Danese PN, Pratt LA, Dove SL, Kolter R. The outer membrane protein, antigen 43, mediates cell-to-cell interactions within Escherichia coli biofilms. Mol Microbiol. 2000 Jul; 37(2):424-32. View abstract
  58. Blum JH, Dove SL, Hochschild A, Mekalanos JJ. Isolation of peptide aptamers that inhibit intracellular processes. Proc Natl Acad Sci U S A. 2000 Feb 29; 97(5):2241-6. View abstract
  59. Hochschild A, Dove SL. Protein-protein contacts that activate and repress prokaryotic transcription. Cell. 1998 Mar 06; 92(5):597-600. View abstract
  60. Dove SL, Hochschild A. Conversion of the omega subunit of Escherichia coli RNA polymerase into a transcriptional activator or an activation target. Genes Dev. 1998 Mar 01; 12(5):745-54. View abstract
  61. Dove SL, Hochschild A. Use of artificial activators to define a role for protein-protein and protein-DNA contacts in transcriptional activation. Cold Spring Harb Symp Quant Biol. 1998; 63:173-80. View abstract
  62. Dove SL, Joung JK, Hochschild A. Activation of prokaryotic transcription through arbitrary protein-protein contacts. Nature. 1997 Apr 10; 386(6625):627-30. View abstract
  63. Dove SL, Smith SG, Dorman CJ. Control of Escherichia coli type 1 fimbrial gene expression in stationary phase: a negative role for RpoS. Mol Gen Genet. 1997 Mar 18; 254(1):13-20. View abstract
  64. Dove SL, Dorman CJ. Multicopy fimB gene expression in Escherichia coli: binding to inverted repeats in vivo, effect on fimA gene transcription and DNA inversion. Mol Microbiol. 1996 Sep; 21(6):1161-73. View abstract
  65. Dove SL, Dorman CJ. The site-specific recombination system regulating expression of the type 1 fimbrial subunit gene of Escherichia coli is sensitive to changes in DNA supercoiling. Mol Microbiol. 1994 Dec; 14(5):975-88. View abstract