Gene expression is a difficult topic for students to learn and comprehend, at least partially because it involves various biochemical structures and processes occurring at the microscopic level. Designer Bacteria, a design-based learning (DBL) unit for high-school students, applies principles of DBL to the teaching of gene expression. Throughout the 8-week unit, students genetically engineer bacteria to meet a need in their own lives. Through a series of investigations, discussions, and design modifications, students learn about the molecular processes and structures involved in gene expression, and how these processes and structures are dependent upon various environmental variables. This article is intended to describe the Designer Bacteria unit and report preliminary results of student progress and performance on pre-unit and post-unit assessments. Teacher experiences and student progress indicate that Designer Bacteria successfully taught core aspects of gene expression through DBL.