Tricia Kiley

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

1989-1990        National Institutes of Health National Service Award

1992-1997         Shaw Scientist Award, Milwaukee Foundation

1993-1998         NSF Young Investigator Award

2004-2006       Vilas Associate Award

2007-present    Fellow, American Academy of Microbiology

2021-present     Fellow, American Association for the Advancement of Science

2022                   Robert Turell UWMF Professorship in Biomolecular Chemistry Leadership

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.

Selected Reviews

• 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:
25450978.

• 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.