Keith M. Derbyshire
    M. smegmatis ESX-1 proteins fused to the yellow fluorescent protein are seen as distinct foci localized to the cell pole.
    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.

Keith M. Derbyshire, Ph.D.

Associate Director for Research and Technology
Director, Division of Genetics
Professor, School of Public Health, Biomedical Sciences
Molecular Genetics of Mycobacteria
Ph.D., Edinburgh University (1983)
Postdoctoral training: Yale University
Fellow of the American Association for Advancement of Science (2018)
Fellow of the American Academy of Microbiology (2019)
(518) 473-6079
Fax: (518) 486-7971

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. To this end, the laboratory utilizes both basic molecular genetic techniques and state-of-the-art genome-wide approaches to determine the genetic architecture, expression and functions of mycobacterial genes.

The current research projects in the laboratory are:

  1. Distributive conjugal transfer (DCT) and genetic exchange in mycobacteria
  2. ESX secretion systems and their role in DCT and cell-cell communication
  3. Genome architecture of mycobacteria and the mechanism of leaderless gene expression
  4. Characterization of the mycobacterial small proteome

To learn more, please visit the Derbyshire and Gray Laboratory.

Select Publications
Sparks IL, Derbyshire KM, Jacobs WR Jr, Morita YS. Mycobacterium smegmatis: The Vanguard of Mycobacterial Research. J Bacteriol. 2023; 205 (1): e0033722. DOI: 10.1128/jb.00337-22
Smith C, Canestrari JG, Wang AJ, Champion MM, Derbyshire KM, Gray TA, Wade JT. Pervasive translation in Mycobacterium tuberculosis. Elife. 2022; Mar 28 (11): e73980. DOI: 10.7554/eLife.73980
Judd JA, Canestrari J, Clark R, Joseph A, Lapierre P, Lasek-Nesselquist E, Mir M, Palumbo M, Smith C, Stone M, Upadhyay A, Wirth SE, Dedrick RM, Meier CG, Russell DA, Dills A, Dove E, Kester J, Wolf ID, Zhu J, Rubin ER, Fortune S, Hatfull GF, Gray TA, Wade JT, Derbyshire KM. A Mycobacterial Systems Resource for the Research Community. mBio. 2021; 12 (2): e02401-20. DOI: 10.1128/mBio.02401-20
Zhu J, Wolf ID, Dulberger CL, Won HI, Kester JC, Judd JA, Wirth SE, Clark RR, Li Y, Luo Y, Gray TA, Wade JT, Derbyshire KM, Fortune SM, Rubin EJ. Spatiotemporal localization of proteins in mycobacteria. Cell Rep. 2021; 37 (13): 110154. DOI: 10.1016/j.celrep.2021.110154
Canestrari JG, Lasek-Nesselquist E, Upadhyay A, Rofaeil M, Champion MM, Wade JT, Derbyshire KM, Gray TA. Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria. Mol Microbio. 2020; 114 (1): 93-108. DOI: 10.1111/mmi.14498
Smith C, Canestrari JG, Wang J, Derbyshire KM, Gray TA, Wade JT. Pervasive Translation in Mycobacterium tuberculosis. 2019;
Gray TA, Derbyshire KM. Blending genomes: distributive conjugal transfer in mycobacteria, a sexier form of HGT. Mol Microbiol. 2018; 108 (6): 601-613.
Clark RR, Judd J, Lasek-Nesselquist E, Montgomery SA, Hoffmann JG, Derbyshire KM3, Gray TA. Direct cell-cell contact activates SigM to express the ESX-4 secretion system in Mycobacterium smegmatis. Proc Natl Acad Sci U S A. 2018; 115 (28): E6595-E660.
Gray TA, Clark RR, Boucher N, Lapierre P, Smith C, Derbyshire KM. Intercellular communication and conjugation are mediated by ESX secretion systems in mycobacteria. Science. 2016; 354 (6310): 347-350.
Shell SS, Wang J, Lapierre P, Mir M, Chase MR, Pyle M, Gawande R, Ahmad R, Sarracino D, Ioerger TR, Fortune SM, Derbyshire KM, Wade JT, Gray TA. Leaderless transcripts and small proteins are common features of the mycobacterial translational landscape. PLOS Genetics. 2015; 11 (11): e1005641.
Gray TA, Krywy JA, Harold J, Palumbo MJ, Derbyshire KM. Distributive Conjugal Transfer in Mycobacteria Generates Progeny with Meiotic-Like Genome-Wide Mosaicism, Allowing Mapping of a Mating Identity Locus. Plos Biology. 2013; 11 (7): e1001602.
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