Biochemistry/molecular biology (BMB) course‐based undergraduate research experiences (CUREs) are part of a growing movement to involve a greater number of undergraduates in authentic research experiences. Positive outcomes of CUREs are manifold, including improvement in scientific aptitude, confidence, and critical thinking skills that make students more likely to become career scientists. Here we describe the structure and outcomes of a one‐semester, senior BMB capstone CURE that pairs two 75‐min weekly discussion/problem‐solving sessions with semester‐long, weekly laboratory research. Within the context of two complex systems (bacterial and influenza infections), students were taught how to approach BMB literature. In the first three weeks of the course, students read and discussed primary literature directly relevant to their laboratory project. Additional literature selected for its demonstration of BMB techniques was presented by students throughout the remainder of the term in an alternating seminar/problem solving format. In the laboratory, all of the students studied homologs of the RNA‐binding protein Hfq, which is small (~11 kDa), thermostable, and present in about half of sequenced bacterial species. All students expressed and purified a previously uncharacterized, wild type Hfq homolog, enabling them to improve their technique with some instructor guidance. Simultaneously, students used databases and primary literature to design independent projects to test their own hypotheses about Hfq from various bacterial species. All pairs of students cloned novel proteins using synthetic biology and successfully purified Hfq at least once. This scaffolded approach to experimentation contextualized fundamental BMB technical skills, boosting understanding of sequence databases, cloning, SDS‐PAGE, protein expression/purification, three‐dimensional protein structure, and activity assays. Final laboratory papers were written using a manuscript submission template from a professional journal and a class‐wide, blinded peer review, furthering the emphasis on an authentic research experience. Students gained an appreciation for the medical impact of basic science and a multidimensional understanding of our discipline. This type of integrated course can be easily customized to emphasize other themes (e.g. cancer) and enhance undergraduate contributions to other original research projects within the time frame of a single semester.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.