Stoddard, Barry

The overall goal of our laboratory is to characterize the structure/function relationships of a variety of enzymatic catalysts at the atomic level. The results of this work are being extended to engineer novel properties onto existing enzyme scaffolds. Most of our particular area of focus is on enzymes that act to modify nucleic acid substrates, and a unifying theme between many of the individual projects is the selection and engineering of these enzymes for targeted genetic applications. The tools employed by our lab are X-ray crystallography, computer modeling, and genetic manipulation of the molecules of interest, combined with biochemical analyses of function. Projects: 1. Structure, function and engineering of intron-encoded homing endonucleases, related rare-cutting endonucleases and closely related 'domesticated' proteins (intron splicing factors, restriction endonucleases, and genetic regulators) 2. Structure, function and engineering of nucleotide salvage enzymes and related enzymology projects. 3. Computational design of novel protein folds and functions (with David Baker, UW) 4. Structural, biochemical and bioinformatic studies of the WhiA protein family in bacterial sporulation and related biological pathways.