A report by the U.S. Environmental Protection Agency found 46% of rivers and streams and 21% of lakes are in poor biological condition (EPA, 2017). In this 5E standards-based inquiry lesson, students actively engage with the natural phenomena of algal blooms through the introduction of the harmful algal bloom (HAB) that occurred in Lake Erie's western basin in the summer of 2011. Students make sense of relationships within aquatic ecosystems, using microcosms (miniature ecosystems) containing phytoplankton and zooplankton, and then communicate their findings through a scientific manuscript. This lesson engages students in the three-dimensional learning identified in the Next Generation Science Standards (NGSS) under the standard of HSLS2, Ecosystems: Interactions, Energy, and Dynamics. More specifically, students address the expectation of HS-LS2-6 when they make sense of how the complex interactions in ecosystems maintain relatively consistent numbers and types of organisms in stable conditions, while changing conditions may result in new ecosystems. This long-term scientific investigation also provides students with opportunities to make sense of aspects of the nature of science, while increasing their science content knowledge and understanding of the practices of science. Evaluation of student work occurs at all stages of the lesson.