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
- Sourice, M., I. Askenasy, P.S. Garcia, Y. Denis, G. Brasseur, P.J. Kiley, B. Py, and C. Aubert. (2023). A Diverged Transcriptional Network for Usage of Two Fe-S Cluster Biogenesis Machineries in the Delta-Proteobacterium Myxococcus xanthus. mBio, 14: e0300122.
- Balderas, D., M. Ohanyan, P.A. Alvarez, E. Mettert, N. Tanner, P.J. Kiley, and V. Auerbuch. (2022). Repression by the H-NS/YmoA histone-like protein complex enables IscR dependent regulation of the Yersinia T3SS. PLoS genetics, 18: e1010321.
- Lakey, B.D., K.S. Myers, F. Alberge, E.L. Mettert, P.J. Kiley, D.R. Noguera, and T.J. Donohue. (2022). The essential Rhodobacter sphaeroides CenKR two-component system regulates cell division and envelope biosynthesis. PLoS genetics, 18: e1010270.
- Lal, P.B., F. Wells, and P.J. Kiley. (2022). Creation of Markerless Genome Modifications in a Nonmodel Bacterium by Fluorescence-Aided Recombineering. Methods in molecular biology (Clifton, N.J.), 2479: 53-70.
- Chowdhury, W.P., K.A. Satyshur, J.L. Keck, and P.J. Kiley. (2021). Minor Alterations in Core Promoter Element Positioning Reveal Functional Plasticity of a Bacterial Transcription Factor. mBio, 12: e0275321.
- Lal, P.B., F. Wells, K.S. Myers, R. Banerjee, A.M. Guss, and P.J. Kiley. (2021). Erratum for Lal et al., "Improving Mobilization of Foreign DNA into Zymomonas mobilis Strain ZM4 by Removal of Multiple Restriction Systems". Applied and environmental microbiology, 87: e0180521.
- Lal, P.B., F. Wells, K.S. Myers, R. Banerjee, A.M. Guss, and P.J. Kiley. (2021). Improving Mobilization of Foreign DNA into Zymomonas mobilis Strain ZM4 by Removal of Multiple Restriction Systems. Applied and environmental microbiology, 87: e0080821.
- Lal, P.B., F.M. Wells, Y. Lyu, I.N. Ghosh, R. Landick, and P.J. Kiley. (2021). Corrigendum: A Markerless Method for Genome Engineering in Zymomonas mobilis ZM4. Frontiers in microbiology, 12: 719621.
- Balderas, D., E. Mettert, H.N. Lam, R. Banerjee, T. Gverzdys, P. Alvarez, G. Saarunya, N. Tanner, A. Zoubedi, Y. Wei, P.J. Kiley, and V. Auerbuch. (2021). Genome Scale Analysis Reveals IscR Directly and Indirectly Regulates Virulence Factor Genes in Pathogenic Yersinia. mBio, 12: e0063321.
- 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.