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
- Lainhart, W, Stolfa, G. and Koudelka, G.B. (2009) Shiga Toxin as a Bacterial Defense against a Eukaryotic Predator, Tetrahymena thermophila, J. Bacteriol. 191 5116-5122
- Watkins, D., Hsiao, C., Woods, K.K., Koudelka, G.B., Williams, L.D., (2008) P22 c2 Repressor-Operator Complex: Mechanisms of Direct and Indirect Readout. Biochemistry 47, 2325-2338.
- Shkilnyj, P. and Koudelka, G.B. (2007) Effect of Salt Shock on the Stability of λimm434 Lysogens, J. Bacteriol., 189:3115-3123.
- McCabe, B.C., Pawlowski, D.R., Koudelka, G.B., (2005) The bacteriophage 434 repressor dimer preferentially undergoes autoproteolysis by intramolecular mechanism. J. Bacteriol., 187 5624-30
- Koudelka, G.B., Hufnagel, LA, Koudelka, A.P. (2004) Isolation, Purification and Characterization of a Repressor from the Toxin-encoding Bacteriophage 933W J. Bacteriol., 186 7659-7669.
- Mauro, S.A., Koudelka, G.B. (2004) Monovalent Cations Direct Sequence Recognition by 434 Repressor, J. Mol. Biol 340 445-457.
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