A computational approach to the study of malate dehydrogenase

Co-Investigator: Kathleen Cornely, Providence College
Co-Investigator: Tyler Stack, Providence College

Scientific Theme: Cancer

Abstract: There are several benefits to replacing traditional labs with Course-based Undergraduate Research Experiences (CUREs). Providing research experience to all students improves motivation, engagement with their classmates and professors, and persistence in STEM. Like any CURE, our current CHM 310 class aims for students to learn how to 1) develop and justify a hypothesis, 2) design appropriate experiments, 3) complete reproducible experimental work, 4) Document their experiments in a laboratory notebook, 5) analyze data and 6) provide conclusions based on the data that support or refute the hypothesis. However, our current CURE is not amenable to a transition to virtual and remote learning. This proposal aims to develop our current CURE in CHM 310 to incorporate virtual methods in a fully remote setting or complement entirely in-person instruction post-pandemic. As part of the Malate Dehydrogenase CURE Community (MCC), we focus on enzyme malate dehydrogenase (MDH) found in central metabolism. Students generate mutants to test the specificity of MDH because MDH utilizes substrates other than malate in specific cancers. In a virtual CURE, students will design mutant MDH enzymes to generate and test a hypothesis using a suite of freely available software programs to characterize the properties of the mutant protein. Ellis Bell, an MCC founder, demonstrated the adaptation of an MDH CURE to fully remote learning. We aim to use his methodology as a model for our specific project done in our CHM 310 class. Given the success of the virtual CURE produced by Ellis Bell, we expect to have similar success teaching undergraduates the computational methods of enzymology, whether we fully shift to remote learning or complement a future course entirely in-person.

Human Health Relevance: The virtual CURE focuses on studying mutations of human malate dehydrogenase, an essential enzyme in central metabolism, and how changes in the enzyme relate to adaptations in the metabolism of cancer. Providing research experience to all biochemistry majors will develop the content knowledge and laboratory skills necessary for our undergraduates to succeed in graduate school, biomedical research, or the clinic.