Engaging middle-school students in scientific inquiry is typically recognized as important, but difficult. Designed to foster learner engagement, this method used an online, problem-based, science inquiry that investigated the West Nile virus during four weeks of collaborative classroom sessions. The inquiry prototype was authored in WISE, the Web-Based Science Inquiry Environment headquartered at UC, Berkeley. Online materials, readings, and class sessions were augmented with interactive electron microscopy images and an introduction to nanoscale science through the ImagiNations Web site at Lehigh University. This approach proved highly engaging and generated design and development guidelines useful to others interested in designing for student engagement in middle school science.