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Introduction
Natural competence, the ability of many bacteria to take up DNA from
their surroundings, raises a number of important questions: How are
inflexible and highly charged DNA molecules transported across
membranes? What environmental or physiological signals trigger this
ability? Is the DNA used primarily as a genetic or a nutritional
resource? Our broad goal is to answer these questions for Haemophilus influenzae,
an important human pathogen and the model system for studies of DNA
uptake in the gamma-proteobacteria. The questions are
interrelated—consideration of biological function guides investigation
of mechanism and regulation, and understanding the mechanism and
regulation helps us understand why cells take up DNA.
We have recently identified the components of the H. influenzae
competence regulon (25 genes in 13 transcription units). We’ve also
found that this regulon is ancestral in many related pathogens
including Escherichia coli and Vibrio cholerae,
suggesting that many more bacteria may be naturally competent than
previously thought. At the heart of the regulon is an entirely novel
mode of regulation by CRP, in which the competence-specific inducer
protein Sxy directs CRP to activate transcription at a new class of CRP
sites. The nutritional signals we’ve identified suggest that DNA is
more valuable for its nucleitides than for its genetic information.
Our ongoing research uses the tools of molecular
biology, bioinformatics and evolutionary biology. We culture bacteria,
run DNA, RNA and protein gels, align sequences and search for motifs,
test DNAs and proteins for interactions, write and run Perl programs,
analyze real-time PCR and microarray results, and even tie DNA down
with laser tweezers (with some help from our physicist friends). You
can read more about our research plans in our grant proposals (what we’re planning), you can read our research blogs to see what we’re currently working on (what we’re doing), and you can read the papers we’ve published (what we’ve done).
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