Laboratory Researct @ HMC
R&T Center
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R&T Center2

Arturo Centurion-Lara, MD
Research Associate Professor, Department of Medicine

Research in this laboratory focuses on Treponema pallidum, the etiologic agent of syphilis. We are studying the mechanisms of immune evasion in T. pallidum in collaboration with Drs. Sheila Lukehart and Wes Van Voorhis. 1. Gene Conversion. We have identified the first mechanism of antigenic variation in syphilis responsible for the generation of tprK diversity. It involves donor cassettes, one expression site and non-reciprocal gene conversion mechanisms. Experimental data demonstrate sequential acquisition of sequence diversity consistent with this mechanism. We are also studying the role of the homologous and non-homologous recombination machinery in T. pallidum to determine their role in the generation of tprK diversity. As a first step, we are using the E. coli recombination machinery to reproduce recombinatorial events between donor sites and the tprK expression site. 2. Phase Variation. We have recently identified “G” homopolymeric repeats in the promoter regions of the tpr genes of the Tpr Subfamilies I and II. It is likely that poly “G” tracts are involved in ON-OFF switch mechanisms of gene expression regulation. Similar structures have been already shown to be regulatory elements in several bacterial species. We have shown that these potential regulatory sequences vary in length within and among T. pallidum isolates. Due to the inability to cultivate T. pallidum in vitro, we are using in-vitro transcription systems and reporter genes (lacZ fusions for ß-galactosidase assays) to study promoter strength and establish correlations with mRNA levels at different time points during infection. 3. Identification of operons/single transcriptional units of the tpr genes. We are defining the boundaries of the tpr transcriptional units and identifying their regulatory elements (promoters, transcriptional start sites, termination structures, repeat sequences). We have found a complex transcriptional pattern of these genes. There is co-transcription of tprJ and tprI as well as of tprG and tprF genes, but we have also identified monocistronic messages in some T. pallidum isolates. The transcriptional starts of these two operons are localized immediately downstream of the “G” homopolymeric repeats in the promoter regions.

In collaboration with Dr. Christina Marra, we are currently studying the genetic markers of T. pallidum strains isolated during the syphilis epidemic in Seatlle.

 

Location: RT 621 (lab)/RT 611 (office)
Phone: (206) 897-5360/ (206) 897-5364
Email:
acentur@u.washington.edu
Department of Medicine, Division of Allergy and Infectious Diseases - Profile

 

 

 

 

 

 

 

 

 

 

Copyright University of Washington - Last Updated 10/26/2011 by Amy Crossman