A Semester‐Long Laboratory in Molecular Biology and Biochemistry Focusing on the Discovery of Novel β‐Lactamase Inhibitors From Streptomyces

Undergraduate laboratory courses should teach not only core experimental skills, but also the relevance of those skills to addressing contemporary scientific challenges. In this course, entitled Biochemistry & Molecular Biology Laboratory, students clone a gene into an expression plasmid, express and purify an enzyme, and perform kinetic assays on the enzyme. The enzyme chosen for this experimental sequence is TEM-1, a β-lactamase enzyme that is a key mediator of resistance to β-lactam antibiotics, such as penicillins. In parallel, the students gain experience in microbiology and natural product extractions by first isolating a Streptomyces species from soil and then screening this isolate for antibiotic activity and the ability to produce compounds that inhibit TEM-1 enzymatic activity. In principle, this research effort could lead to the discovery of either a novel strain of Streptomyces clavuligerus, which produces the important TEM-1 inhibitor clavulanate, or another Streptomyces strain producing a novel TEM-1 inhibitor. Thus, students are introduced to a pressing problem in contemporary medicine, antibiotic resistance, while they participate in discovery-driven efforts to solve that problem. Incorporation of discovery-based objectives into the laboratory sequence gives students individualized datasets to analyze, thereby promoting the development of student analytical skills. In addition, during the course, the students enhance their scientific writing skills through a series of peer-reviewed writing assignments and ultimately complete a formal journal-style article, in which they communicate their research findings. Overall, this course compares favorably with a course-based undergraduate research experience (CURE) course, as gauged by student-reported learning gains and overall course assessment.