Project Summary/Abstract The overall goal of this proposal is to understand how organisms as diverse as humans and the fruit flies use the same molecules to decide when and where cells will divide, especially when they are needed to repair damaged tissues. The specific focus of this application is a protein that is highly conserved from insects to humans, and appears to act specifically in the adult gut to support stem cell renewal of this tissue over the organism's lifespan. Despite its apparent importance to gut homeostasis, the protein has not been the subject of sustained study. Our preliminary data indicate that acts as a signaling hub that receives inputs from phospholipids and in turn delivers regulatory outputs onto two highly conserved pathways broadly involved in human health and disease. We are very excited to leverage the strength of our data to understand how this protein coordinates these various roles within intestinal stems cells in Drosophila. Our own cells have a version of this protein, so we believe that our work will shed light on mechanisms that support our stem cells too.