Sheldon Park Laboratory

The Sheldon Park Laboratory uses knowledge of protein structure-function relationship to engineer improved or novel protein molecules, for use in biotechnology and therapy. Researchers use a rational approach, incorporating homology modeling and molecular dynamics simulation to design proteins. These proteins are then tested empirically with biochemical and cellular assays. The Park lab engineered the first monomeric streptavidin (mSA) by incorporating elements of tetrameric and dimeric streptavidin homologs. Streptavidin-biotin interaction is broadly used in many biotechnology applications, mSA can be incorporated into other protein constructs to introduce a biotin binding module and enable stable noncovalent interaction with biotin. Researchers currently use mSA with a rationally designed protein-based nanoparticle to convert weak to moderate binders (engineering or naturally found) to a 60-mer spherical oligomer (NP60) with ultrahigh affinity/avidity, enhancing the function of the molecule in biosensing or therapeutic applications. In addition to NP60, researchers are developing a novel oligomer combining a natural bacterial protein with an engineered molecule to provide an alternative presentation mode. Molecules displayed on assembly templates include carbohydrate binding proteins to detect various glycan moieties on the cell surface, and single domain antibodies with therapeutic potential. The glycan binding proteins are engineered in vitro characterization using modeling. Assembling engineered proteins on the NP scaffold helps improve the proteins’ binding properties through multivalent interaction. Ultimately, these large-scale structures will be used as reagents in research and therapy to elucidate essential biological processes at the cell surface, and provide therapeutic relief.