Professor of Microbiology
Phone:(206) 685-1390, (206) 543-0177, (206) 543-7045
Office Location: Health Sciences, J-117A
Campus Box: 357735
Dr. Leigh received his Ph.D. at the University of Illinois, and did his postdoctoral work at Massachusetts Institute of Technology in the Department of Biology.
Leigh’s lab combines an evolutionary perspective with a focused molecular approach. We work with Methanococcus maripaludis, a member of the methanogenic Archaea. The methanogens evidently originated early in the evolution of life. Today they occupy anaerobic habitats ranging from hydrothermal vents to animal digestive tracts, where most species grow on hydrogen and carbon dioxide and produce methane as a catabolic product. With excellent growth characteristics, effective genetic tools, and well-developed genome-based technologies, M. maripaludis has become the “E. coli of the Archaea”.
Projects in the lab focus on methanogenesis, nitrogen regulation, and systems biology. We recently identified a protein complex supporting electron bifurcation, a novel mechanism of energy conservation in methanogenesis. We discovered two novel mechanisms for the regulation of nitrogen fixation, one involving transcriptional repression and the other involving direct binding of regulatory proteins to nitrogenase.
The lab is also collaborating to determine global regulatory patterns at the transcriptome and proteome levels and to develop a regulatory network model for the methanogens.
Leigh is also a participating faculty member in the Astrobiology Program at the University of Washington.
Wisedchaisri, G., D. M. Dranow, T. J. Lie, J. B. Bonanno, Y. Patskovsky, S. A. Ozyurt, J. M. Sauder, S. C. Almo, S. R. Wasserman, S. K. Burley, J. A. Leigh, and T. Gonen. 2010. Structural underpinnings of nitrogen regulation by the prototypical nitrogen-responsive transcriptional factor NrpR. Structure 18: 1512-1521.
Costa K. C., P. M. Wong, T. Wang, T. J. Lie, J. A. Dodsworth, I. Swanson, J. A. Burn, M. Hackett, and J. A. Leigh. 2010. Protein complexing in a methanogen suggests electron bifurcation and electron delivery from formate to heterodisulfide reductase. Proc. Natl. Acad. Sci. USA 107:11050-11055.
Lie, T. J., E. L. Hendrickson, U. M. Niess, B. C. Moore, A. K. Haydock, and J. A. Leigh. 2010. Overlapping repressor binding sites regulate expression of the Methanococcus maripaludis glnK1 operon. Molecular Microbiol. 75:755-762.
Hendrickson, E. L., A. K. Haydock, B. C. Moore, W. B. Whitman, and J. A. Leigh. 2007. Functionally distinct genes regulated by hydrogen limitation and growth rate in methanogenic Archaea. Proc. Natl. Acad. Sci. USA 104:8930-8934.
Dodsworth, J. A. and J. A. Leigh. 2006. Regulation of nitrogenase by 2-oxoglutarate-reversible, direct binding of a PII-like nitrogen sensor protein to dinitrogenase. Proc. Natl. Acad. Sci. USA 103:9779-9784.