Professor Shahir Rizk recently published in Scientific Reports of the Nature Publishing Group. This effort began in a post-doctoral position at the University of Chicago and finished here at IU South Bend. As main author, Rizk collaborated with several researchers with connections to the University of Chicago, the New York University Langone Medical Center, and the New York University School of Medicine - scientists that he continues to collaborate with. Rizk explains the article's theme in the following paragraph, but you can read the abstract and full paper by clicking here.
Many diseases result from a mutation that causes an enzyme deficiency. This typically impairs the function of an essential enzyme, leading to disease manifestation. In many cases, the mutation impairs the ability of the enzyme to adopt the correct 3D structure required for proper function. This article addresses the question: How can we bring an enzyme that has been disrupted by mutation back to life? We focused on Isocitrate Dehydrogenase I, a metabolic enzyme that is mutated in a large percentage of individuals with brain tumors. The goal was to restore function to the mutant enzyme by trying to force it to adopt the correct 3D structure. We used a technique called phage display, which allowed us to engineer an antibody fragment that binds to the natural 3D structure of the enzyme. When added to the mutant enzyme, the engineered antibody fragment was able to restore natural function to the mutant enzyme. While this study was done in the test tube, it is a fist step in the design of "activator molecules" that can hopefully help restore function to a large number of mutant enzymes.