Cottrell Scholar Awards - 2016
Structural Characterization of Substrate Promiscuity in Bacterial Sortases
Researchers are actively learning how to use bacterial enzymes - called sortases - as tools to modify proteins and peptides from other organisms. The molecules created in this way could serve as new leads for therapeutics and basic research tools due to the fact that they often possess chemical and biological attributes not found in nature.
John M. Antos, assistant professor of chemistry, Western Washington University, hopes to break new ground in the use of bacterial sortases for protein engineering. “An important challenge for modern chemists is developing strategies for manipulating proteins in precise and novel ways, thereby enabling the construction of proteins with new functions,” Antos says.
Specifically, Antos and his students are trying to uncover the basis for differences in reactivity among sortases from different bacterial species. Their work will include the chemical synthesis of unique peptides (very short proteins) that mimic natural sortase substrates, and will ultimately involve elucidating the three-dimensional structure of the sortase enzymes themselves. Antos envisions that these fundamental studies will form the foundation of new and exciting protein engineering applications that rely on these bacterial enzymes.
For the education component of the Cottrell Scholar Award, Antos will use his research to develop a discovery-driven laboratory experiment for an undergraduate organic laboratory course. Students will participate in a multi-week drug discovery exercise that includes computer modeling, organic synthesis, and in vitro enzyme studies to design small-molecule sortase inhibitors with applications in the treatment of tooth decay.
“We will complement this lab module by piloting the use of a flipped classroom strategy to boost student engagement and create more opportunities for active learning in the associated organic chemistry lab lecture,” he says. A “flipped classroom” approach requires students to listen to lectures on their own time – through You Tube or some other service – and then spend class time engaged in research and discussion.