M.Sc., University of Calcutta, India
Ph.D., University of Illinois College of Medicine
phone: (336) 716-1124
“I will strive to foster an environment that allows free and open exchange of ideas and is conducive to the growth of the new students and postdoctoral fellows as successful and independent scientists. I will attempt to expose them to a combination of the established and newly emerging hypotheses and techniques, thereby promoting to their intellectual and scientific development.” Transcriptional Regulation, Functional Genomics of Host-Pathogen Interactions and Biofilms.
Our research program utilizes an integrated approach to investigate the mechanism and importance of differential gene expression and the roles of newly identified factors in Bordetella pathogenesis. Bordetella species are small aerobic, Gram-negative bacteria that colonize the respiratory tracts of humans and other animals. B. pertussis, the human pathogen results in the disease known as Whooping cough while B. bronchiseptica mainly infects animals and causes a variety of respiratory diseases. The bvgAS locus coordinately regulates the majority of the known products involved in Bordetella pathogenesis. As opposed to the traditional view of mediating a biphasic transition, the Bvg-regulatory system appears to control an entire spectrum of distinct gene expression states e.g. the Bvg+, Bvgi and the Bvg- phases.
We are interested in understanding the molecular basis of transcriptional control by the facultative regulatory protein BvgA. One of the projects in the laboratory involves analyses of regulatory intricacies of expression of bipA, the first identified Bvgi–phase specific gene. The signal-dependent regulatory profile of bipA is determined by the interplay of transcriptional activation and repression. Expression of bipA in response to modulating signals is unusual in that this gene is most highly expressed at a point along the Bvg-regulatory continuum where the activity and the level of BvgA-P is predicted to be at an intermediate level.
We are utilizing the emerging field of functional genomics to identify new vaccine candidates and virulence factors and to study species-specific differences among Bordetella. We have identified a number of ORFs which have homology to several proteins that are known to play a role in virulence of other bacteria including outer membrane proteins and proteins involved in colonization. The gamut of genes will be characterized for their precise role in infection and persistence in the upper respiratory tract. One such gene we have identified is bcfA, a paralog of bipA. We have shown that BipA and BcfA have overlapping role in colonization of mouse trachea. Currently we are in the process of determining the precise role of BipA and BcfA in Bordetella pathogenesis and to examine their protective role against Bordetella infections.
Recently, we have discovered a previously unknown virulence strategy for Bordetella. We have demonstrated that during the persistent stage of infection in the mouse respiratory tract, Bordetella exist as sessile communities known as biofilms. Biofilms are structured aggregates of sessile bacterial cells that are encased in a self-produced polymeric organic matrix. The biofilm mode of existence is believed to contribute to the pathogenesis of a number of bacterial infections. We hypothesize that development of nasopharyngeal biofilms in humans allow B. pertussis to escape immune defenses thereby leading to the carrier state and serve as reservoirs for transmission to unvaccinated infants and children. We believe that the ability of B. pertussis to form biofilms in mice implicates a role for this mode of existence during human infections. Current biofilm research in the laboratory is focused on the role of bacterial and host factors in contributing to biofilm development both in vitro and in the mouse model.