Multiple calls for reform of foundational science course at the undergraduate level have been made in recent years. Nevertheless, change has been slow at most universities and the impact of such reform efforts has often been limited. In this presentation, I will summarize and discuss what we have learned through the investigation of our own efforts to revamp an introductory chemistry course for science and engineering majors. This course (Chemical Thinking) seeks to create a learning environment in which students actively grapple with central ideas, engage in the analysis of relevant phenomena, develop and evaluate models of systems of interest, and generate arguments and explanations based on evidence. The course is being implemented by instructional teams comprised of a lead faculty and 10 to 20 undergraduate and graduate learning assistants working in large collaborative learning spaces with hundreds of students. In this talk, I will discuss the challenges that we are facing to meaningfully affect student learning and our own conceptualizations of teaching and learning in these complex learning environments.