This project develops new methods for preparing cells that secrete insulin in response to elevated glucose concentrations. The ultimate objective is to provide reliable sources of cells that can be used to treat Type 1 diabetes. The effort draws on the complementary expertise of laboratories at City of Hope and Caltech, and has yielded new methods for the culture and differentiation of pancreatic progenitor cells. The laboratory of Teresa Ku at City of Hope has developed new techniques for the study of single progenitor cells in culture, and is using these techniques in conjunction with a new class of engineered extracellular matrix proteins designed in the laboratory of David Tirrell at Caltech. Success in generating glucose-sensitive secretion of insulin has been achieved with cells derived from mice. Ongoing experiments are extending these methods to human cells.