SSP’s New Student Research Project in Biochemistry and its Larger Significance by Michael A. Weiss, M.D., Ph.D., M.B.A., SSP ’74, Chair of Biochemistry, Case Western Reserve University School of Medicine Proteins are among the key building blocks of life. SSP’s new student research project in biochemistry, designed by Profs. Mark Hall and Stefan Paula of Purdue University, focuses on the principles and applications of protein structure and enzymatic catalysis. Both are fundamental features of modern biology. Specifically, SSP students will conduct research on the protein Cdc14 present in almost all animals and funguses. Cdc14 catalyzes the cleavage of “phosphoester flags” from amino-acid side chains, a reaction that serves as a “signaling” mechanism within an organism. Inhibiting such signaling—by inhibiting Cdc14—has important potential applications, from human cancer treatment to protecting agricultural crops from diseases. The choice of Cdc14 has deep historical resonance, as it was first identified in landmark genetic studies by Nobel Laureate Leland Hartwell (2001 Prize in Physiology or Medicine). Prof. Hall’s own laboratory has made seminal recent contributions to understanding and harnessing the signaling pathway regulated by Cdc14. During the Summer Science Program in Biochemistry, 36 gifted high-school students will learn together the principles and practice of protein structure, including three-dimensional molecular modeling, mechanisms of enzymatic catalysis, and its inhibition. In parallel, each team of three students will study the Cdc14 protein unique to a particular fungal pathogen. The teams will isolate their Cdc14 enzyme, identify its preferred molecular targets, create a computer model of its structure, and characterize the inhibition of its activity by a set of candidate inhibitors. They will then design improved, customized inhibitor molecules for future testing. Each step in the project will allow students to develop and test hypotheses based on their observations. Finally, each team’s data will be archived in public databases accessible to other scientists. As they learn the practice of experimental science, these gifted high-school students will also be contributing to the long-term global effort to foster a second Green Revolution. Boosting agricultural productivity is necessary to increase the carrying capacity of Earth and avoid a “Malthusian challenge” in the coming decades. Safe, effective and eco-friendly crop protection will be critically important. Part of the solution to preventing fungal infestations— and feeding humanity—may turn out to be the new Cdc14 inhibitors characterized and designed by teenagers at the Summer Science Program.
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