This new biochemistry laboratory course moves through a progression of experiments that generates a platform for guided inquiry-based experiments. RNase One gene is isolated from prokaryotic genomic DNA, expressed as a tagged protein, affinity purified, and tested for activity and substrate specificity. Student pairs present detailed explanations of materials and methods and the semester culminates in a poster session. Experimental plans take into account the expense and time required to move from gene isolation to enzyme assays. This combination of instructor-guided and student-designed experiments is a manageable foray into guided inquiry-based learning in a biochemistry laboratory course, while providing a cohesive story and context for individual experiments.Keywords: guided-inquiry, RNase one, experimental design.Students typically retain only 20% of the content of any given course [1,2], and most college students, even high achieving students, continue to think in the same ways they thought prior to taking their courses [3]. These results give pause for thought to even the most gifted teacher. The reasons for such low content retention output are various but include the failure to create learning environments that help students learn how to think for themselves and learn on their own, assess stated learning objectives other than rote memorization, and actively construct their own learning [1,2]. Active learning is particularly important for achieving transferrable, critical thinking, communication, and other ''soft'' skills that students need for living and working in a globalized world [4].Inquiry-based learning environments are more effective than traditional lecture or recipe style laboratory courses. Sixth and seventh grade students who learned physics by way of inquiry-based pedagogies outperformed eleventh and twelfth grade students who learned physics in traditional lecture formats on assessments of their grasp of physics concepts [5]. If learning is about changing the way students think, that is, changing the way they approach problems, solve problems, and make decisions in a complex, globalized world, then new learning pedagogies seem to be in order. To move toward more active, constructivist learning pedagogical models, BIO2010 [6] calls for the way scientists think through a research question to serve as a model for student learning. The inquiry based biochemistry lab curriculum described below aims to begin this kind of pedagogical change.Moving from ''cookbook'' style laboratory classes to inquiry-based or guided-inquiry based experiences can provide challenges for a faculty member instigating this change. Three such challenges are covering a required set of techniques, acquiring equipment and supplies to support a variety of experiments, and guiding an unstructured experience [7][8][9]. The semester described here combines the research process, student delivered laboratory materials and methods, two guided inquiry-based experiments, and a culminating final poster session to provide context to...