One of the challenges of teaching Cell Biology is helping students understand important research methods used to study cells.  The goal of understanding cell biology methods is especially challenging in courses without a laboratory component.  When studying cells, determining the location of a protein is important for understanding the protein's cellular function.  In this lesson, upper-division Cell Biology students will learn about two commonly used methods for protein localization: 1) immunoblotting after differential centrifugation, and 2) immunofluorescence microscopy.  They will work in small groups to answer questions in a problem set written in the spirit of Process-Oriented Guided Inquiry Learning (POGIL).  Students will explore key points of the two methods and then apply their knowledge to the analysis of protein localization data from the primary literature.  Analyzing protein localization data will help students develop the ability to “apply the process of science”, which is one of the Vision and Change core competencies.