Position title: Professor and Chair
Phone: (608) 262-6632
4204C Biochemical Sciences Building
440 Henry Mall, Madison, WI 53706
• 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
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
Perform a customized PubMed literature search for Dr. Kiley.
• Carey JN, Mettert EL, Roggiani M, Myers KS, Kiley PJ, Goulian M (2018) Regulated
Stochasticity in a Bacterial Signaling Network Permits Tolerance to a Rapid Environmental
Change. Cell 173(1):196-207.e14 (PMC5866230)
• Mettert EL, Kiley PJ (2017) Reassessing the Structure and Function Relationship
of the O Sensing Transcription Factor FNR. Antioxid Redox Signal. 2017 Nov 14
• Beauchene NA, Mettert EL, Moore LJ, Keleş S, Willey ER, Kiley PJ (2017)
O availability impacts iron homeostasis in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A.
• Beauchene NA, Myers KS, Chung D, Park DM, Weisnicht AM, Keleş S, Kiley PJ (2015)
Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons.
MBio 6(6):e01947-15 (PMC4676285)
• Mettert EL, Kiley PJ (2015) How Is Fe-S Cluster Formation Regulated? Annu.
Rev. Microbiol. 69:505-26
• Myers KS, Park DM, Beauchene NA, Kiley PJ (2015) Defining bacterial regulons
using ChIP-seq. Methods 86:80-8 (PMC4577457)
• Tolla DA, Kiley PJ, Lomnitz JG, Savageau MA (2015) Design principles of a
conditional futile cycle exploited for regulation. Mol Biosyst 11(7):1841-9 (PMC4470783)
• Mettert EL, Kiley PJ (2015) Fe-S proteins that regulate gene expression.
Biochim. Biophys. Acta 1853(6):1284-93 (PMC4390428)
• Mettert EL, Kiley PJ. Coordinate regulation of the Suf and Isc Fe-S cluster
biogenesis pathways by IscR is essential for viability of Escherichia coli. J Bacteriol.
2014 Dec;196(24):4315-23. doi: 10.1128/JB.01975-14. Epub 2014 Sep 29 (PMC4248859)
• Park DM, Kiley PJ. The influence of repressor DNA binding site architecture on
transcriptional control. MBio. 2014 Aug 26;5(5):e01684-14. doi:
• Miller HK, Kwuan L, Schwiesow L, Bernick DL, Mettert E, Ramirez HA, Ragle JM,
Chan PP, Kiley PJ, Lowe TM, Auerbuch V. IscR is essential for Yersinia
pseudotuberculosis type III secretion and virulence. PLoS Pathog. 2014 Jun
12;10(6):e1004194. doi: 10.1371/journal.ppat.1004194. eCollection 2014 Jun
• Park DM, Akhtar MS, Ansari AZ, Landick R, Kiley PJ. The bacterial response
regulator ArcA uses a diverse binding site architecture to regulate carbon
oxidation globally. PLoS Genet. 2013;9(10):e1003839. doi:
10.1371/journal.pgen.1003839. Epub 2013 Oct 17 (PMC3798270)
• Myers KS, Yan H, Ong IM, Chung D, Liang K, Tran F, KeleÅŸ S, Landick R, Kiley
PJ. Genome-scale analysis of Escherichia coli FNR reveals complex features of
transcription factor binding. PLoS Genet. 2013 Jun;9(6):e1003565. doi:
10.1371/journal.pgen.1003565. Epub 2013 Jun 20 (PMC3688515)
• Rajagopalan S, Teter SJ, Zwart PH, Brennan RG, Phillips KJ, Kiley PJ. Studies
of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding
specificity. Nat Struct Mol Biol. 2013 Jun;20(6):740-7. doi: 10.1038/nsmb.2568.
Epub 2013 May 5 (PMC3676455)
• Giel JL, Nesbit AD, Mettert EL, Fleischhacker AS, Wanta BT, Kiley PJ.
Regulation of iron-sulphur cluster homeostasis through transcriptional control of
the Isc pathway by [2Fe-2S]-IscR in Escherichia coli. Mol Microbiol. 2013
Feb;87(3):478-92. doi: 10.1111/mmi.12052. Epub 2012 Oct 17 (PMC4108476)
• Nesbit AD, Fleischhacker AS, Teter SJ, Kiley PJ. ArcA and AppY antagonize IscR
repression of hydrogenase-1 expression under anaerobic conditions, revealing a
novel mode of O2 regulation of gene expression in Escherichia coli. J Bacteriol.
2012 Dec;194(24):6892-9. doi: 10.1128/JB.01757-12. Epub 2012 Oct 12 (PMC3510566)
• Fleischhacker AS, Stubna A, Hsueh KL, Guo Y, Teter SJ, Rose JC, Brunold TC,
Markley JL, Munck E, Kiley PJ. Characterization of the [2Fe-2S] cluster of
Escherichia coli transcription factor IscR. Biochemistry. 2012 Jun
5;51(22):4453-62. Epub 2012 May 24 (PMC3447993)