The Zika ThreatASM Acts to Counter Zika Virus Outbreak.
Dr. Taylor received his B.A. degree from the State University of New York at Buffalo in 1976. He received his Ph.D. degree in Biological Sciences from the University of Maryland, Baltimore County in 1984 where he studied mechanisms of bacterial gene expression in response to environmental stimuli. He did his postdoctoral training at Harvard Medical School where he began his work on the identification and regulation of virulence determinants in the pathogenic bacterium, Vibrio cholerae. In 1986 Dr. Taylor joined the faculty in the Department of Microbiology at the University of Tennessee Medical School in Memphis and in 1993 moved to the Microbiology and Immunology Department at Dartmouth Medical School as an Associate Professor. He is currently Professor of Microbiology and Immunology and director of M2P2 at Dartmouth College.
Vibrio cholerae is a Gram-negative bacterium that colonizes the human intestinal tract causing severe, potentially lethal, diarrhea in infected individuals. V. cholerae represents a paradigm of bacterial pathogens. It elaborates a plethora of virulence factors including a potent exotoxin, adherence colonization factors, secreted enzymes, and additional toxins that contribute to its pathogenesis. The expression of the genes that encode these factors is exquisitely coordinated in response to the environment the bacterium encounters, such as certain regions of the host intestine. All of these mechanisms represent models for bacterial pathogenesis and interaction with the host in general. Dr. Taylor's laboratory focuses on the molecular mechanisms of adherence and colonization, protein secretion with respect to the elaboration of adherence factors and toxin, and coordinate expression of the corresponding genes. His goals are to understand the processes in enough detail to design better methods to control infection by defining immunogens for improved vaccine development, improving ways to grow strains for manufacture of killed whole cell vaccines, and by identifying new targets to be considered for the design of novel antibiotics.
The research projects in Dr. Taylor's lab can be divided into two broad areas. The first deals with interaction between the bacterium and the host. Bacteria colonize hosts through the use of surface appendages termed fimbriae or pili. Vibrio cholerae potentially utilizes several pili types, outer membrane proteins, and secreted proteins for this process. All of these represent potential immunogens. He has focused on a pilus termed TCP for toxin coregulated pilus. For this structure, he employs molecular biology, structural biology and immunology techniques to investigate the function of specific domains in the colonization process, and the efficacy for their use as vaccine components. Aspects of the pilus study also involve the macromolecular assembly of this structure by studying the functions of various cloned gene products. He is finding that the process requires novel molecules that have homologs in various extracellular protein secretion processes that may be inhibitable by antimicrobial compounds. Another surface component that has potential as an immunogen is the LPS layer that covers the surface of the bacterium. Monoclonal antibodies are being used to investigate protective epitopes on this structure.
The second major area of investigation is to understand the mechanisms by which V. cholerae senses the environment and induces expression of virulence genes. Specifically he is investigating the mechanism of activation of the tcp genes that encode the pilus, and the ctx genes that encode the cholera toxin. This activation works through a regulatory cascade that includes membrane sensing and DNA binding proteins termed ToxR and TcpP which in turn regulate the expression of a cytoplasmic activator protein, ToxT, that is also required for expression of many virulence genes. Expression of tcpP occurs in response to environmental parameters and is regulated by the AphA and AphB proteins, which represent the top of the regulatory cascade. Expression of all the virulence genes he studies is repressed by the H-NS protein. He is employing a variety of techniques to understand very specific details of how these regulatory proteins act at their respective promoters, and how they actually sense environmental signals. This work should lead to an understanding of the signals that trigger gene expression and how the process can be altered during infection.
*Text and image borrowed from http://www.dartmouth.edu/~rktlab/Taylor_Lab/Welcome.html