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This paper describes our work in a clinical-based teacher preparation in which pre-service teachers attempted to implement inquiry-based science instruction to help students make sense of genetic engineering. We engaged a small cohort of pre-service teachers in science methods coursework embedded in the classroom of a more experienced high school science teacher. We utilized developmental models of professional practice that outline the complexity inherent in professional knowledge to analyze video-recordings of the instructional practices of three teachers implementing a unit plan. Three teaching practices emerged as fundamental to inquiry-based science instruction: (1) conceptual goals of the lesson, (2) questioning practices teachers enact, and (3) student-centered sense-making. Trajectories through which professional teachers develop advanced practices that support inquiry-based instruction are discussed.