PhD, Stanford University, 1981
Our laboratory is broadly interested in enzymatic mechanisms in DNA biochemistry. Our current research is focused on a process known as transformational recombination which occurs in the major human pathogen, Streptococcus pneumoniae. S. pneumoniae is a naturally transformable bacterium that is able to take up DNA from its environment and incorporate this exogenous DNA into its own chromosome. This process serves as a general mutational mechanism which in recent years has allowed S. pneumoniae to develop resistance to various classes of antibiotics.
We have isolated and analyzed many of the proteins which have been shown by genetic analysis to be involved in transformational recombination, or required for S. pneumoniae viability in general. These include the S. pneumoniae RecA protein (a DNA recombinase), the SsbA and SsbB proteins (two single stranded DNA binding proteins), the MmsA protein (a DNA helicase), the RecO and RecR proteins (two recombinase accessory proteins), the DprA protein (a likely recombination accessory protein), and the YqgF protein (a potential DNA junction binding protein). Our continuing investigations of the coordinated action of these key proteins are aimed at determining the biochemical mechanism of transformational recombination, and will provide insight into the molecular basis for the development of antibiotic resistance in Streptococcus pneumoniae and related human pathogens.