We developed an advanced, year-long course sequence in eukaryotic cell and molecular biology in order to increase conceptual understanding. Three years of historical data from a one semester, traditional-lecture, senior cell and molecular biology course (n = 237) were compared with 3 years of data collected from the year-long course sequence (n = 176). There were significant content gains for the students who enrolled in the course sequence when pre- and post-assessments were compared (p < 0.0001). There was an association between earning a C or better in the course sequence and 70% or higher in the post-assessment instrument (p < 0.05). Final course grades for Bio 135A were calculated from three open ended exams and the percentage of correct answers on the clicker questions. For Bio135B, final grades were calculated from three open ended exams, clicker responses, a seven-page literature review on an environmental carcinogen and its effects on signal transduction pathways, and a formal presentation of one of the research articles they used in the literature review. The students who took the second semester of the course passed at higher rates than the students who enrolled in the traditional-lecture course (p < 0.05). Clicker answers to the research problem sets and the final course grades correlated significantly for both semesters of the course sequence (p < 0.01). We conclude that conceptually-connected learning gains can be obtained when the content is taught in a format that includes short lectures and group work to solve research questions.