Susan H. Fisher, Ph.D.
Professor of Microbiology
72 East Concord Street
Office: R515; 617-638-5498
Lab: R520; 617-638-5498
B.S. Washington University
M.A. Washington University
Ph.D. Tufts Medical School
The research in my laboratory focuses on global systems which regulate the expression of enzymes involved in nitrogen metabolism in response to nutrient availability in the sporulating Gram-positive soil bacterium Bacillus subtilis. Genes expressed at high levels during nitrogen-limited growth are controlled by two related proteins, TnrA and GlnR, that bind to similar DNA sequences under different nutritional conditions. Although the nitrogen signal regulating the activity of the GlnR and TnrA protein is not known, genetic studies indicate that the wild-type glutamine synthetase protein is required for the transduction of this signal to the TnrA and GlnR proteins.
We have shown that the feedback-inhibited form of glutamine synthetase inhibits TnrA DNA binding activity in vitro. This indicates that glutamine synthetase most likely regulates TnrA by a protein-protein interaction. We are using genetic techniques and biochemical approaches (i) to characterize the interaction between glutamine synthetase and TnrA and (ii) to detemine whether glutamine synthetase also interacts with GlnR.
- Wray, L.V.,Jr, A.E. Ferson, K. Rohrer and S.H. Fisher. 1996. TnrA, a transcriptional factor required for global nitrogen regulation in Bacillus subtilis. Proc.Natl.Acad.Sci.(USA). 93: 8841-8845.
- Wray, L.V.Jr., J.M. Zalieckas, A.E. Ferson and S.H. Fisher. 1998. Mutational analysis of the TnrA binding sites in the Bacillus subtilis nrgAB and gabP promoter regions. J. Bacteriol. 180:2943-2949.
- Fisher, S. H. 1999. Regulation of nitrogen metabolism in Bacillus subtilis: vive la difference! Mol. Microbiol. 32:223-232.
- Wray, L.V., Jr., J. M. Zalieckas, and S. H. Fisher. 2000. Purification and in vitro activities of the Bacillus subtilis TnrA transcription factor. J.Mol.Biol.300:29-40.
- Belitsky, B.R., L.V.Wray, Jr. S.H. Fisher, D.E. Bohannon, and A.L. Sonenshein. 2000. Role of TnrA in nitrogen source-dependent repression of Bacillus subtilis glutamate synthase gene espression. J. Bacteriol. 182:5939-5947.
- Wray, L.V. Jr., Zalieckas, J.M., Fisher, S.H. 2001. Bacillus subtilis glutamine synthetase controls gene expression through a protein-protein interaction with transcription factor TnrA. Cell. 107(4):427-435.
- Fisher, S.H., Wray, L.V. Jr. 2002. Bacillus subtilis 168 contains two differentially regulated genes encoding L-asparaginase. J. Bacteriol. 184(8):2148-2154.
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