The overall goal of our laboratory is to characterize the structure/function relationships of a variety of enzymatic catalysts at the atomic level. Much of this work is being extended into efforts to engineer novel structures and properties onto existing protein and enzyme scaffolds. A unifying theme between many of the individual projects is the selection and engineering of these enzymes for targeted therapeutic and/or biotech/industrical 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.
Hallinan JP, Doyle LA, Shen BW, Gewe MM, Takushi B, Kennedy MA, Friend D, Roberts JM, Bradley P, Stoddard BL. Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces. Commun Biol. 2021 Oct 29;4(1):1240. doi: 10.1038/s42003-021-02766-y. PMID: 34716407; PMCID: PMC8556268.
Forsberg KJ, Schmidtke DT, Werther R, Uribe RV, Hausman D, Sommer MOA, Stoddard BL, Kaiser BK, Malik HS. The novel anti-CRISPR AcrIIA22 relieves DNA torsion in target plasmids and impairs SpyCas9 activity. PLoS Biol. 2021 Oct 13;19(10):e3001428. doi: 10.1371/journal.pbio.3001428. PMID: 34644300; PMCID: PMC8545432.
Luyten YA, Hausman DE, Young JC, Doyle LA, Higashi KM, Ubilla-Rodriguez NC, Lambert AR, Arroyo CS, Forsberg KJ, Morgan RD, Stoddard BL, Kaiser BK. Identification and characterization of the WYL BrxR protein and its gene as separable regulatory elements of a BREX phage restriction system. Nucleic Acids Res. 2022 May 2:gkac311. doi: 10.1093/nar/gkac311. Epub ahead of print. PMID: 35511079.