Interdisciplinary Initiatives Program Round 11 - 2022
William Weis, Structural Biology, Photon Science Directorate, and Molecular & Cellular Physiology
Alexander Dunn, Chemical Engineering
Wnt/β-catenin signaling controls the differentiation and renewal of stem cells during development and maintenance of adult animal tissues. Wnts are growth factors that bind to cell surface receptors, which produces changes in gene expression that govern cellular growth and differentiation. Mutations in components in this pathway underlie many diseases, including cancers by producing uncontrolled cell growth. Although the core molecular components and the basic circuit of the pathway have been established, the molecular mechanism underlying Wnt/β-catenin signaling is not understood, which has hindered development of therapeutics that target this pathway. Our recent data indicate that this pathway uses an unexpected and novel mechanism for transmembrane signaling. In this project, we will use advanced optical microscopy and single molecule imaging in combination with engineered ligands to define the precise mechanisms that control Wnt/β-catenin signaling.