Credentials: Molecular genetics and biochemistry of oxygen regulated gene expression and transcription activation
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.
• Mettert EL, Kiley PJ. Fe-S proteins that regulate gene expression. Biochim
Biophys Acta. 2014 Nov 20. pii: S0167-4889(14)00416-9. doi:
10.1016/j.bbamcr.2014.11.018. [Epub ahead of print] Review. PubMed PMID:
• Dietrich LE, Kiley PJ. A shared mechanism of SoxR activation by redox-cycling
compounds. Mol Microbiol. 2011 Mar;79(5):1119-22. doi:
10.1111/j.1365-2958.2011.07552.x. Epub 2011 Jan 31. PubMed PMID: 21338412.
• Fleischhacker AS, Kiley PJ. Iron-containing transcription factors and their
roles as sensors. Curr Opin Chem Biol. 2011 Apr;15(2):335-41. doi:
10.1016/j.cbpa.2011.01.006. Epub 2011 Feb 1. Review. PubMed PMID: 21292540;
PubMed Central PMCID: PMC3074041.
Perform a customized PubMed literature search for Tricia Kiley
- Ong, W.K., D.K. Courtney, S. Pan, R.B. Andrade, P.J. Kiley, B.F. Pfleger, and J.L. Reed. (2020). Model-driven analysis of mutant fitness experiments improves genome-scale metabolic models of Zymomonas mobilis ZM4. PLoS computational biology, 16: e1008137.
- Banerjee, R., E. Weisenhorn, K.J. Schwartz, K.S. Myers, J.D. Glasner, N.T. Perna, J.J. Coon, R.A. Welch, and P.J. Kiley. (2020). Tailoring a Global Iron Regulon to a Uropathogen. mBio, 11: .
- Corless, E.I., E.L. Mettert, P.J. Kiley, and E. Antony. (2020). Elevated Expression of a Functional Suf Pathway in Escherichia coli BL21(DE3) Enhances Recombinant Production of an Iron-Sulfur Cluster-Containing Protein. Journal of bacteriology, 202: .
- Hooker-Romero, D., E. Mettert, L. Schwiesow, D. Balderas, P.A. Alvarez, A. Kicin, A.L. Gonzalez, G.V. Plano, P.J. Kiley, and V. Auerbuch. (2019). Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated infection. PLoS pathogens, 15: e1008001.
- Carey, J.N., E.L. Mettert, D.R. Fishman-Engel, M. Roggiani, P.J. Kiley, and M. Goulian. (2019). Phage integration alters the respiratory strategy of its host. eLife, 8: .
- Lal, P.B., F.M. Wells, Y. Lyu, I.N. Ghosh, R. Landick, and P.J. Kiley. (2019). A Markerless Method for Genome Engineering in Zymomonas mobilis ZM4. Frontiers in microbiology, 10: 2216.
- Kim, J., M. Tremaine, J.A. Grass, H.M. Purdy, R. Landick, P.J. Kiley, and J.L. Reed. (2019). Systems Metabolic Engineering of Escherichia coli Improves Coconversion of Lignocellulose-Derived Sugars. Biotechnology journal, 14: e1800441.
- Mettert, E.L., and P.J. Kiley. (2018). Reassessing the Structure and Function Relationship of the O Sensing Transcription Factor FNR. Antioxidants & redox signaling, 29: 1830-1840.
- Carey, J.N., E.L. Mettert, M. Roggiani, K.S. Myers, P.J. Kiley, and M. Goulian. (2018). Regulated Stochasticity in a Bacterial Signaling Network Permits Tolerance to a Rapid Environmental Change. Cell, 175: 1989-1990.
- Carey, J.N., E.L. Mettert, M. Roggiani, K.S. Myers, P.J. Kiley, and M. Goulian. (2018). Regulated Stochasticity in a Bacterial Signaling Network Permits Tolerance to a Rapid Environmental Change. Cell, 173: 196-207.e14.