PROJECT SUMMARY – CELL BIOLOGY CORE Cell Biology has been a component of the DRTC since its inception in 1977. It has taken many forms over the past 40 years, most recently focusing on studies of pancreatic islets and beta cells. However, in recent years and, continuing in this application, the Cell Biology Core has been expanded to also include studies of adipocytes, hepatocytes, and innate and adaptive immune cells from diabetic and non-diabetic humans and mice. The Core provides a broad range of services in cell-based systems to elucidate the roles of islet endocrine cells, adipocytes, hepatocytes and immune cells in health and disease with an emphasis of studies using primary cells from humans and mice. In addition, with this renewal, the Core will provide sophisticated models in zebrafish to study in vivo and in real time the effect of the diabetogenic environment (insulin resistance, insulin deficiency) on metabolically active cells, including islets, hepatocytes, kidney cells, and innate immune cells. The Core provides advice on study design, methods, and data interpretation. Because many of the techniques are new to investigators, the Core also provides direct hands-on support and training to ensure the successful and timely completion of experiments. This Core is centered at the University of Chicago and the University of Illinois at Chicago. The two groups meet regularly and have developed standard operating procedures to ensure that Users receive quality support for their studies. The Core also has an ongoing commitment to training and has trained investigators, fellows, students and research technicians in the procedures of the Core. The Cell Biology Core is an integral part of the DRTC, and thus synergizes with the Physiology Core by facilitating diabetes-based research on primary cells and tissues from mice and humans. Moreover, it allows discoveries made in the Genetics and Genomics Core to be tested in a biological context. The Aims of the Core are: 1. To provide pancreatic islets, adipocytes, hepatocytes, and innate and adaptive immune cells (e.g. macrophages, neutrophils, T-cells) from normal and diabetic humans, mice, and zebrafish, as well as insulinoma, pre-adipocyte, and iPSC (from non-diabetic patients and patients with monogenic forms of diabetes) cell lines. 2. To continuously improve new experimental approaches (e.g. use of cells derived from iPSCs) that can provide better physiological and pathophysiological context for discovery. 3. To actively promote interaction and collaboration among DRTC members and attract outside investigators to the field of diabetes research by highlighting the advantages of diabetes-relevant experimental systems for studies of cross-cutting themes and questions.