Faculty
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Harshey, Rasika
Professor in Molecular Genetics & Microbiology
E-mail Website Main Office: NMS 2.118
Phone: 471-6881 Alternate Office: NMS 2.232
Phone: 471-6799 Mailing Address:
The University of Texas at Austin - ICMB
1 University Station A5000
100 E. 24th St.
Austin, TX 78712-1095
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Research Summary:
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 sensing mechanisms. When Salmonella are propagated on a solid agar surface, they differentiate into metabolically distinct swarmer cells capable of migrating rapidly over the agar surface using flagella. Moisture is critical for surface motility. We have discovered that the chemotaxis system plays a mechanical role in generating surface wetness and promoting motility, and that the flagellum can sense wetness to regulate its own biogenesis. 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. The questions we are addressing may lead to the discovery of unifying principles that govern the secretion of flagellar components and virulence factors.
Research Images:
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 |
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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 |
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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 |
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Publications:| 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. | | 2007 | Wang Q, Zhao Y, McClelland M, Harshey RM, The RcsCDB signaling system and swarming motility in Salmonella enterica serovar typhimurium: dual regulation of flagellar and SPI-2 virulence genes, J Bacteriol 189:8447-8457. | | 2006 | Mariconda S., Wang Q, and Harshey, R. M., A mechanical role for the chemotaxis system in swarming motility, Mol. Microbiol 188:1590-602. | | 2005 | Yin Z, Harshey RM. , Enhancer-independent Mu transposition from two topologically distinct synapses., Proc Natl Acad Sci U S A. 102:18884-9. | | 2005 | Wang Q, Suzuki A, Mariconda S, Porwollik S, Harshey RM. , Sensing wetness: a new role for the bacterial flagellum., EMBO J. 24:2034-42. | | 2004 | T.K. Au, S. Pathania, and R.M. Harshey, True reversal of Mu integration, EMBO J. 23:340 -3420. |
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