Patricia J. Kiley
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Professor574 Medical Sciences Center Office: (608) 262-6632 |
Education
- B.S. 1979, University of Massachusetts;
- Ph.D. 1987, University of Illinois (S. Kaplan);
- Postdoctoral, 1987-90, University of Wisconsin (W. Reznikoff).
Honors & Awards
- Shaw Scientist Award, 1992.
- National Science Foundation Young Investigator Award, 1993
- Vilas Associate Award, 2004
- Fellow, American Academy of Microbiology, 2007
Research Interests
We are interested in the signaling pathways and gene expression programs
organisms use to respond to changes in the levels of oxygen in the
environment. Oxygen is essential for life of aerobic organisms but can also
act as a poison by causing oxidative damage to proteins, lipids and DNA.
Therefore, an organism’s ability to respond efficiently and precisely
to oxygen is critical to its survival.
Our approach is to focus on the mechanisms of key transcription factors
in Escherichia coli that regulate this single-celled microbe’s lifestyle
in different oxygen environments. E. coli is an excellent model organism to
investigate because of the rich history of study in this area, and because
of the facile genomic, molecular genetic, biochemical and physiological
approaches that can be exploited in this bacterium. Our findings also
impact on understanding the integration of global regulatory networks
with signal specific regulators to efficiently control gene expression
in response to various inputs.
We are studying two transcription factors, IscR and FNR, that exploit
Fe-S metal centers in the global response to oxygen. FNR contains an oxygen labile
[4Fe-4S] cluster and functions as an oxygen sensor. IscR contains a [2Fe-2S]
cluster and senses Fe-S cluster availability via cluster synthesis. Our
results indicate that the properties of Fe-S proteins enable exquisite
control of their function as transcription factors.
We are also discovering how these transcription factors reprogram gene
expression to allow E. coli to adapt to oxygen limiting environments similar
to that found in the gut, which is an important habitat of this bacterium.
We have used global gene expression profiling (microarrays) to uncover
the roles of IscR and FNR in controlling transcription under these conditions.
As expected, we found that E. coli responds to oxygen deprivation by synthesizing
proteins that provide alternate mechanisms for conserving energy when
oxygen is not available. However, we also discovered new functions that are
upregulated under anaerobic conditions and we hypothesize that these contribute
in a novel way to anaerobic growth.
Publications of Note
Giel, J.L., D. Rodionov, M. Liu, F. R. Blattner, and P. J. Kiley. 2006. IscR-dependent gene expression links iron-sulfur cluster assembly to the control of O2-regulated genes in Escherichia coli. Mol. Microbiol. 4:1058-1075.
Mettert, E, and P. J. Kiley. 2005. ClpXP-dependent proteolysis of FNR upon loss of its O2-sensing [4Fe-4S] cluster. J. Mol. Biol. 354:220-232.
Kang, Y., K. Derek Weber, Y. Qiu, P.J. Kiley and F. R. Blattner. 2005. Genome wide expression analysis indicates that FNR of Escherichia coli K12 regulates a large number of genes of unknown function. J. Bacteriol. 187:1135-1160
Sutton, V.R, T. Patschkowski, and P.J. Kiley. 2004. Superoxide destroys the [2Fe-2S]2+ cluster of FNR from Escherichia coli. Biochemistry. 43:791-798.
Sutton, V. R., E. L. Mettert, H. Beinert, and P.J. Kiley. 2004. Kinetic analysis of the oxidative conversion of the [4Fe-4S]2+ cluster of FNR to a [2Fe-2S]2+ cluster. J. Bacteriol 186: 8018-8025.
Lamberg, K. E., C. Luther, K.D. Weber and P.J. Kiley. 2002. Characterization of activating region 3 from Escherichia coli. J. Mol. Biol. 315:275-283.
Moore, L. and P.J. Kiley. 2001. Characterization of the dimerization domain in the FNR transcription factor. J. Biol. Chem. 276: 45744-45750.
Schwartz, C. J., J. L. Giel, T. Patschkowski, C. Luther, F. J. Ruzicka, H. Beinert and P. J. Kiley. 2001. IscR, an Fe-S cluster containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins. PNAS 98: 14895-14900.
Selected Reviews
Kiley P.J. and G. Storz. 2004. Exploiting thiol modifications. PLOS Biology 2:1714-1717.
Kiley, P. J. and H. Beinert. 2003. Role of Fe-S clusters in sensing and regulating bacterial growth. Current Opinion in Microbiology. 6:181-185.
Sutton, V.R., and P.J. Kiley. 2003 Anaerobic isolation and assays for the transcription factor FNR from Escherichia coli. Methods in Enzymology. 370: 300-12.
Patschowski, T., D. M. Bates and P. J. Kiley. 2000. Mechanism for sensing and responding to oxygen deprivation in prokaryotic organisms. "Bacterial Stress Responses" ASM Press Washington, D. C. p. 61- 78.
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University
of Wisconsin - Department
of Biomolecular Chemistry
First published: 01/01/05 Last updated:
9/29/05 Email Biomolecular Chemistry
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