Preservice elementary teachers face many challenges in learning how to teach science effectively, such as engaging students in science, organizing instruction, and developing a productive learning community. This paper reports on several iterative cycles of design-based research aimed at fostering preservice teachers' principled reasoning around these problems of practice through modeling-centered scientific inquiry. The first design cycle introduced preservice teachers to modeling and simulation software tools in an effort to advance their understanding of science and technology; the second used an instructional framework embodying modeling-centered inquiry to advance their views of effective science teaching and their lesson-planning practices; the third engaged preservice teachers in analyzing and modifying curriculum materials using reform-based criteria to foster effective curriculum materials use. Outcomes from these iterations indicate that the preservice teachers were most likely to advance their knowledge and practices within a coherent approach that focused on a core scientific practice such as modeling-centered inquiry, provided opportunities to unpack and apply robust tools such as reform-based instructional frameworks, and addressed their perceived problems of practice. The findings from this set of approaches are compared to others in an effort to point toward promising future directions for effective science teacher education.