Lab Research Focus
My laboratory is involved in a number of projects all of which revolve around issues of microbial diversity and bacterial pathogenesis. The M proteins of group A streptococci and the PspA and PspC proteins of Streptococcus pneumonia are two families of surface proteins that are important virulence factors. Both are components of prospective vaccines so the scope of their diversity and the mechanisms generating it must be understood on a practical level for the vaccines to be effective. The pathogenetic role of these proteins is intimately connected to their mode of evolution. Both families consist of mosaic proteins, indicating that recombination has been one contributor to the generation of diversity. Additionally, tandem repeat units are common among members of the families and some diversity is generated by slipped strand mispairing which causes the insertion or deletion of repeat units. Mechanisms of variation in these important surface proteins are under study in projects that span fields of molecular evolution, molecular epidemiology, microbial pathogenicity and natural selection.
More recently, my laboratory has begun studies of diversity at the genome level in collaboration with ACGT at Perkin-Elmer/ABI and with The Institute for Genomic Research. Under a diversity genome sequencing project, a complete second genome of S. pneumoniae and selected regions of 14 additional genomes will be sequenced. Some regions were chosen to represent genes in which selection during evolution is neutral, while others will represent genes upon which there is positive or diversifying selection. The latter should exhibit greater polymorphism and perhaps equivalent levels of non-synonymous and synonymous substitutions, while the former would be expected to be fairly conserved (limited polymorphic sites) and substitutions would be weighted towards synonymous. These genomic studies have prompted a collaboration in the development of microarray technology to look at all genes simultaneously on a DNA chip. DNA chip technology has enormous potential for understanding microbial diversity and aspects of microbial gene expression as well.
|
|
|
