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image of Keith M. Derbyshire

Keith M. Derbyshire

Research Scientist, Wadsworth Center,

Faculty Member, Wadsworth School of Laboratory Sciences
Molecular Genetics

Professor, School of Public Health, Biomedical Sciences

Ph.D., Edinburgh University (1983)
Postdoctoral training, Yale University

E-mail: keith.derbyshire@health.ny.gov

The Esx-1 secretion apparatus is localized to the cell poles of M. smegmatis. When Esx-1 structural proteins from either M. tuberculosis or M. smegmatis are fused to the yellow fluorescent protein, and cells visualized by fluorescence microscopy, the proteins are localized to a cell pole. Thus, the Esx-1 structural apparatus has a unique cellular location.

Research Interests

Mycobacterium tuberculosis is a leading cause of death by an infectious agent. It is estimated that one-third of the world’s population is infected with M. tuberculosis and that 1.6 million people die of tuberculosis every year. Its deadly synergistic association with HIV, and the appearance of MDR and XDR strains, exacerbate the global health problems associated with the disease. A comprehensive understanding of the biology of this organism is critical for the identification of novel drug targets, for the development of vaccines, and for determining how it evades the host immune system. This requires the development of basic molecular techniques to determine the genetic and biochemical basis of pathogenesis and drug resistance.

The focus of Dr. Derbyshire's laboratory is the process of conjugal DNA transfer, which results in the lateral transfer of DNA between bacterial species, and is primarily responsible for the spread of genes encoding virulence and antibiotic resistance. We have identified a novel DNA transfer system in the non-pathogenic model organism Mycobacterium smegmatis. The goals of the laboratory are to characterize the mechanism of DNA transfer and to determine its role in the biology of mycobacteria. Notably, a 30 kb genetic locus in M. smegmatis is essential for DNA transfer, and encodes a secretory apparatus called Esx-1. This secretion system is highly conserved among mycobacteria and, most relevantly, Esx-1 mutants of M. tuberculosis are attenuated. Thus, by exploiting DNA transfer as a molecular genetic tool, we can elucidate the mechanism of Esx-1 secretion, and determine its role in both regulation of DNA transfer and M. tuberculosis virulence.

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Contact Information

Phone 518-473-6079
Fax 518-486-7971
E-mail: keith.derbyshire@health.ny.gov