Research InterestsThe Bavoil laboratory studies the pathogenesis of the obligate intracellular pathogen, Chlamydia, and its bacteriophages. Specific research areas include:
· Chlamydia type III secretion: Genomic analysis has revealed that type III secretion genes of Chlamydia are dispersed in several genomic clusters, a likely consequence of the unique evolutionary path of these organisms. We have hypothesized that through subversion of host signal transduction, type III secreted virulence effector proteins may be responsible for a range of phenotypes including intracellular survival, modulation of apoptosis, up-regulation of cellular transporters, acquisition of lipids from the Golgi and mitochondria, and signaling for late differentiation. Ongoing projects include the characterization of type III secretion, contact-dependent replication and development, and the identification and functional characterization of type III secreted effector proteins across Chlamydia species.
· Chlamydia bacteriophages: A major focus is the study of phiCPG1, a bacteriophage that infects a Chlamydia caviae strain (GPIC) infectious to guinea pigs, and is distantly related to the coliphage phiX174. PhiCPG1 causes developmental arrest in replicating chlamydiae and induces their lysis and that of the chlamydial inclusion. A significant finding through genomic analysis of Chlamydia pneumoniae strain AR39 was the isolation of the genome of a bacteriophage closely related to phiCPG1 (phiAR39). Fragments of the phage genome are also found integrated in the genomes of C. caviae and C. pneumoniae. These findings have brought renewed momentum to investigations of the impact of phage infection on chlamydial infection and disease. Moreover, the existence of chlamydiaphages represents a unique opportunity for the development of phage-based genetics in Chlamydia, a major area of research in the laboratory.
· Polymorphic membrane protein family: Genome sequencing has revealed pmp gene families of between 9 and 21 members in Chlamydia sp., the latter representing nearly 15% of the genomic coding capacity. We have expressed all 9 Pmps of C. trachomatis, purified epitope-tagged recombinant polypeptides and produced monospecific polyclonal and monoclonal antibodies. Analysis of specific antibody in male, female and chronically infected patients with genital infection has revealed differential responses to a subset of Pmps cross-sectionally and longitudinally. These and other observations are globally consistent with a proposed role for the Pmp family in antigenic variation and suggest that these proteins are important determinants of pathogenicity. We aim to identify mechanisms of differential pmp expression and antigenic variation at the cellular level. Other ongoing studies include investigations in animal models and topological and functional analyses.
· Comparative genomics: The laboratory is part of a consortium with The Institute for Genomic Research (TIGR) and the University of British Columbia for a broad Chlamydia comparative genomics project (Taxogenomics) developed by Drs. Tim Read and Garry Myers. The project includes the sequencing of six new genomes of the Chlamydiaceae (Simkania, Waddlia, C. pneumoniae Koala, C. suis, C. pecorum and C. psittaci). Genomic information from all species will then be used to construct a gene array (Taxochip) which will allow the identification of new isolates and the isolation of new virulence genes by subtraction. Publications
Chlamydia: Genomics and Pathogenesis. 2006. Bavoil & Wyrick (editors), Horizon Press, Inc. Norwich, UK. |
