The long-term goals of the Forsyth Department of Molecular Genetics are to determine the molecular mechanisms of bacterial pathogenesis, particularly in oral diseases. Understanding host–pathogen interactions is essential for developing successful interventions and preventive treatments.
Several investigators in the Department are involved in the molecular and physiological characterization of bacterial virulence factors from Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Streptococcus mutans. An ongoing project to identify essentially all human oral bacterial species, including those that have not yet been cultivated, has determined by 16S rRNA sequence comparisons that nearly 600 species may inhabit the oral cavity. More than half were identified as novel species. At least some of these "new" species likely represent unrecognized pathogens. To determine the association of individual species with oral diseases and health, the Department has developed a DNA microarray system that can be used to identify more than 300 of the most common species on a single microscope slide.
Using this technology, the Department created a new one-of-a-kind core service for the research community. The Forsyth Microbial Identification Microarray Service (MIM) enables the rapid identification of bacterial species in clinical samples. The first service offering, Human Oral Microbe Identification Microarray (HOMIM), will focus on detection of bacterial profiles from the oral cavity. Researchers can use this service to compare bacterial associations in health vs. disease, monitor the effects of therapy on the oral ecology and perform microbial perturbation studies. Information about the service can be found online at www.forsyth.org/mim.
The Department is also working to determine the molecular and genetic bases of bacterial biofilm development, in particular the relationship between biofilm formation and the pathogenicity of Porphyromonas gingivalis. The switch from a benign, surface-attached state, in which P. gingivalis functions as a commensal organism, to a proliferating, destructive state is central to the virulence of this opportunistic pathogen.
The Department is also conducting clinical studies that focus on the microbiological bases of health and oral diseases, such as initial periodontitis, adult periodontitis, refractory periodontitis, acute necrotizing ulcerative gingivitis, caries of the primary and secondary dentitions, and noma (a facial gangrene that affects malnourished children in developing countries). In other work, our investigators are studying the correlation of vaginal infections with premature or preterm births.
With the genome sequences of many bacteria now available, we are entering the exciting era of functional genomics – assigning function to the thousands of newly discovered unique genes. Typically, up to 40% of a genome contains genes of unknown function. Speculation on their role in the life of a bacterium ranges from gene regulation to activities required for bacterial survival within the human host. Future work in the Department will logically extend to defining these functions through genetics, molecular biology, microarray analysis, and bioinformatics. Mining the genomes of the organisms we study for new virulence genes will extend the repertoire of targets that can be exploited for therapeutic interventions.
Bruce J. Paster, Ph.D., Department Head
Tsute Chen, Ph.D.
Mary Ellen Davey, Ph.D.
Floyd E. Dewhirst, D.D.S., Ph.D.
Jacques Izard, Ph.D.
Anne C. R. Tanner, B.D.S., Ph.D.
POST-DOCTORAL FELLOW
Christine Albert-Sequi, Ph.D.
Eleni Kanasi, D.D.S., MS EPID
Eleftheria Papadopoulou, D.D.S.
Mohammad Dahlan, D.D.S.
