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Faculty
Rasika Harshey
Professor in Molecular Genetics & Microbiology
Email:
rasika@uts.cc.utexas.edu
Website
Main Office:
NMS 2.118
Phone:
(512) 471-6881
Alternate Office:
NMS 2.232
Alt. Phone:
(512) 471-6799
Mailing Address
The University of Texas at Austin
Section of Molecular Genetics and Microbiology
2506 Speedway Stop A5000
Austin ,TX 78712-1191
Research Summary
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.
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