Professor in Molecular Genetics & Microbiology
Main Office: NMS 2.118
Phone: (512) 471-6881
Alternate Office: NMS 2.232
Phone: (512) 471-6799
The University of Texas at Austin
Section of Molecular Genetics and Microbiology
2506 Speedway Stop A5000
Austin, TX 78712-1191
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Research Lab Students:
- Jang, Sooin - Graduate Student
- Kim, Hyo Kyung - Graduate Student
- Lee, Jaemin - Graduate Student
- Lou, Zheng - Graduate Student
- Nieto, Vincent - Graduate Student
- Partridge, John - Graduate Student
- Choi, Wonyoung - Post Doctoral
- Saha, Rudra - Post Doctoral
We have two major research interests: DNA transposition and Bacterial Signaling & Motility. (1) DNA transposition is central to the propagation of phage Mu (our model system) as it is to retroviruses. The integration mechanism of both viruses is remarkably similar. Retroviral integration is followed by DNA repair, while Mu integration has a choice between repair and replication, depending on the phase of its life cycle. Despite extensive research, answers to three important questions in Mu biology, which are intimately related to retroviral integration, have remained elusive. These are: (i) the regulatory decision between repair and replication of a common transposition intermediate, (ii) the mechanism by which Mu avoids integrating into itself, and (iii) how Mu chooses target sites in vivo. We are addressing all three questions both in vitro and in vivo using a combination of molecular genetics and biochemistry. We expect to extend these studies to mammalian cells to use the ubiquitous target delivery protein of Mu to eventually design site-specific gene delivery vectors. (2) Swarming is a specialized form of flagella-driven surface motility displayed by several bacterial genera, which shares features with other surface phenomenon such as biofilm formation and host invasion. Swarming bacteria exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that this group resistance occurs at a cost to cells directly exposed to the antibiotic. We are currently exploring the mechanism of this resistance, which has relevance to the adaptive antibiotic resistance of bacterial biofilms. We have also recently discovered that in our model organisms E. coli and Salmonella, the signaling molecule cycli-di-GMP inhibits chemotaxis by interacting with the flagellar motor to control motor speed and direction. This finding has implications for biofilm formation, and has opened up a new window into a sensory role for the flagellum.
Swarming colony of E. coli - This beautiful pattern was made by bacteria 'swarming' on the surface of agar using flagellar motility. Gene expression patterns during swarming are giving us a window into pathogenicity, where bacterial colonization of surface tissues promotes virulence.
Dr. Harshey's Lab
Bacterial Flagella - Bacteria propagated on the surface of agar 'differentiate' into swarmer cells with increased flagella, among other features, which allows efficient colonization of a solid surface.
Dr. Harshey's Lab
Topology of a 3-site DNA transposition synapse - Interaction of 3 distant DNA sites (L and R ends in blue and Enhancer in red) in a specific interwrapped topology promotes oligomerization and activation of the transposase of phage Mu (not shown). Mu is the most efficient transposon known.
Dr. Harshey's Lab
|2010||K. Paul. V. Nieto, W. C. Carliquist, D. F. Blair and R. M. Harshey, The c-di-GMP-binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a 'backstop break' mechanism, Mol. Cell. 38:128-139.|
|2010||W. Choi and R. M. Harshey, DNA repair by a transposase: the cryptic endonuclease activity of phage Mu transposase is required for post-integration repair, Proc. Natl. Acad. Sci. USA. 107:10014-10019.|
|2010||M. Butler, Q. Wang and R. M. Harshey, Cell density and mobility protect swarming bacteria against antibiotics, Proc. Natl. Acad. Sci. USA. 107:3776-3781.|
|2010||J. Ge, Z. Lou and R. M. Harshey, Immunity of replicating Mu to self-integration: a novel mechanism employing MuB protein, Mobile DNA 1(1):8.|
|2009||Q. Wang and R. M. Harshey, Rcs signaling-activated transcription of rcsA induces strong anti-sense transcription of upstream fliPQR flagellar genes from a weak intergenic promoter: regulatory roles for the anti-sense transcript in virulence and motility, Mol. Microbiol 74:71-84.|
|2008||J. Ge and R. M. Harshey, Congruence of in vivo and in vitro insertion patterns in hot E. coli gene targets of transposable element Mu: Opposing roles of MuB in target capture and integration, J. Mol. Biol. 380:598-607.|
|2008||U. Attmannspacher, B. Scharf and R. M. Harshey, FliL is essential for swarming: motor rotation in absence of FliL fractures the flagellar rod in swarmer cells of Salmonella enterica, Mol. Microbiol 68:328-341.|
|2007||Yin Z, Suzuki A, Lou Z, Jayaram M, Harshey RM, Interactions of phage Mu enhancer and termini that specify the assembly of a topologically unique interwrapped transpososome, J Mol Biol 372:382-396.|
|2005|| Yin Z, Harshey RM. , Enhancer-independent Mu transposition from two topologically distinct synapses., Proc Natl Acad Sci U S A. 102:18884-18889.|
|2005|| Wang Q, Suzuki A, Mariconda S, Porwollik S, Harshey RM. , Sensing wetness: a new role for the bacterial flagellum., EMBO J. 24:2034-2042.|
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