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 nucleotides 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).