Research Summary
The research in the Koudelka lab is focused around two central themes:
Mechanisms of DNA Sequence Recognition:
Understanding the mechanisms used by regulatory proteins in recognizing specific DNA sequences remains one of the most important areas of study in biology. This process requires that the protein be able to seek out and recognize its particular binding sequence amidst the presence of an overwhelming number of potential non-specific binding sites. We seek to uncover the intimate biochemical and thermodynamic underpinnings of DNA sequence recognition.
Evolution of Bacteriophage-encoded Exotoxins
Phages encoding exotoxin genes are found ubiquitously within bacteria isolated from the environment. In the context of humans, these exotoxins cause diseases ranging from cholera to diphtheria to enterohemorrhagic diarrhea. However, the frequency of occurrence of the genes encoding any particular exotoxin gene in bacteriophage and/or lysogens far exceeds the number of potential animal hosts. These observations suggest that humans and other susceptible mammals are not the primary “targets” of these toxins. We are exploring the hypothesis that exotoxins arose in bacteria as part of an antipredator defense mechanism.
Selected Publications
- Stolfa, G., and Koudelka, G.B., (2012) Entry and Killing of Tetrahymena by Bacterially Produced Shiga toxin, mBio, in press.
- Harris, L.A., Watkins, D., Williams, L.D., and Koudelka, G.B. (2012) Indirect Readout of DNA Sequence by P22 Repressor: Roles of DNA and Protein Functional Groups in modulating DNA Conformation, J. Mol. Biol., http://dx.doi.org/10.1016/j.jmb.2012.10.008.
- Bullwinkle, T.J., Samorodnitsky, D., Rosati, R.C. and Koudelka, G.B. (2012) DNA binding specificity determinants of 933W repressor, PLOS One, 7: e34563. doi:10.1371/journal.pone.0034563.
- Pawlowski , D.R., Raslawsky, A., Siebert, G., Metzger, D.J., Koudelka, G.B., Karalus, R.J. (2011) Identification of Hylemonella gracilis as an antagonist of Yersinia pestis persistence. Journal of Bioterrorism & Biodefense, S3:004 doi:10.4172/2157-2526.S3-004.
- Bullwinkle, T.J., and Koudelka, G.B. (2011) The Lysis-Lysogeny Decision of Bacteriophage 933W: A 933W Repressor-Mediated Long Distance Loop Has No Role in Regulating 933W PRM Activity J. Bacteriol. 193, 3313-3223.
- Watkins, D., Mohan, S., Koudelka, G.B., Williams, L.D., (2010) Sequence Recognition of DNA by Protein-Induced Conformational Transitions. J. Mol. Biol., 396, 1145-64.
- Lainhart, W., Stolfa, G., Koudelka, G.B. (2009) Shiga Toxin as a Bacterial Defense against a Eukaryotic Predator, Tetrahymena thermophila, , J. Bacteriol., 191, 5116-5122.
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