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.