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.
Shen BW, Quispe JD, Luyten Y, McGough BE, Morgan RD, Stoddard BL. Coordination of phage genome degradation versus host genome protection by a bifunctional restriction-modification enzyme visualized by CryoEM. Structure. 2021 Jun 3;29(6):521-530.e5. doi: 10.1016/j.str.2021.03.012. Epub 2021 Apr 6. PMID: 33826880; PMCID: PMC8178248.