Rasika M. Harshey
We have two major research interests. (1) DNA-protein interactions in Mu transposition. Many cancer-causing retroviruses including HIV recombine with their host genomes in a manner similar to that used by transposable phage Mu. Assembly of a functional Mu transposase tetramer requires binding of the protein to Mu ends and also to a distantly located enhancer element. Several nucleoprotein complexes called transpososomes have been identified along the transposition pathway. Our current research goal is to understand the architechture of these transpososomes, why the enhancer remains associated with them until the completion of transposition, how target DNA is delivered to this complex, and what the similarities and differences are between the Mu and HIV integration systems. A combination of molecular genetics, biochemistry, and structural studies is being pursued. (2) Swarmer- cell differentiation in Salmonella typhimurium: a model for understanding surface signal transduction and pathogenesis. When this bacterium is propagated on a solid agar surface it differentiates into a specialized swarmer cell which is longer and has more flagella than a vegetative cell. Swarmer cells display a group surface motility that enables them to rapidly colonize the agar surface. The swarming colony lives within a biofilm. We have discovered that under these conditions, the well-known chemotaxis system is not required for chemotaxis, but rather for surface signal transduction. Microarray analysis is revealing interesting parallels between the biogenesis of flagella and that of needle-structures during swarming. Needle structures are distinct organelles that resemble flagella, but are specialized delivery vehicles for virulence proteins during infection of a host. Our experiments are aimed at understanding the molecular mechanism of this new pathway of signal transduction, investigating the similarities and differences between moving and adherent biofilms, as well using swarming as a model system for the analysis of virulence protein secretion.
Sensing wetness: A new role for the bacterial flagelllum. Q. Wang, A. Matsuura, S. Mariconda, S. Porwollik and R. M. Harshey. 2005. The EMBO Journal . In press.
Gene expression patterns during swarming in Salmonella typhimurium: genes specific to surface growth and putative new motility and pathogenicity genes. Q. Wang, J. G. Frye, M. McClelland and R. M. Harshey. 2004. . Mol. Microbiol. 52: 169-187.
Bacterial motility on a surface: many ways to a common goal. R. M. Harshey. 2003. Ann. Rev. Microbiol. 57: 249-273.
Path of DNA within the Mu transpososome: Transposase interactions bridging two Mu ends and the transposition enhancer trap five DNA supercoils. S. Pathania, M. Jayaram and R. M. Harshey. 2002. Cell, 109 : 425-436.
Salmonella enterica swarming mutants with altered biofilm forming abilities: surfactin inhibits biofilm formation.J. R. Mireles II, A. Toguchi and R. M. Harshey. 2001. The Journal of Bacteriology . 183: 5848-5854. The Mu enhancer is functionally asymmetric both in cis and in trans: topological selectivity of Mu transposition is enhancer independent. H. Jiang and R. M. Harshey 2001. J. Biol. Chem. 276: 4373-4381.
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