Leigh Lab : Research
Research
J o h n    L e i g h    L a b

University of Washington Department of Microbiology
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Email the Director :
John Leigh, Ph.D.


Research : Overview

Our lab studies the species Methanococcus maripaludis, a member of the methanogenic Archaea. Our fascination with this organism stems in part from its representation of the third branch of life. As microorganisms that differ from the Bacteria and the Eucaryotes, the Archaea are ripe for discovery. Within the Archaea, the methanogens are important anaerobes in a variety of habitats. Methanococcus maripaludis is a superb model because of its excellent laboratory growth behavior, a robust set of genetic tools, and a complete genome sequence.
Much of the lab studies nitrogen regulation. A novel repressor, known only in certain methanogens and a few other Archaea, governs the expression of genes for nitrogen metabolism. How this repressor functions is an area of intense study. Another novel mechanism regulates the activity of nitrogenase, the enzyme that fixes nitrogen. Here is our current model for nitrogen regulation in M. maripaludis:
Regulation Model></center>
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Model for nitrogen regulation in Methanococcus maripaludis. The repressor NrpR regulates transcription of the nif operon, glnA, and other genes by binding to inverted repeat operators. NifI1 and NifI2, PII nitrogen sensor subfamilies encoded in the nif operon, control nitrogenase activity by an unknown mechanism. Proteins encoded by genes are represented by shapes.


The lab is also actively involved in global regulation. One project is investigating the role of hydrogen (the electron-donating energy source) in regulating mRNA and protein levels in M. maripaludis. Approaches include continuous culture in chemostats, expression array analysis, and proteomic analysis as well as traditional molecular methods. Continuing genetic tool development is another thrust of the lab.
We are also interested in methanogenic Archaea in the context of Astrobiology. Methanogenesis probably evolved early on earth and is a likely metabolism of any life that might exist on Mars or Europa. Several members of the lab participate in the University of Washington's Astrobiology Program.

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