Membrane contact sites enable communication and coordination between the various cellular organelles. However we still do not know what are all the existing contact sites, what are the protein tethers holding membranes together and how the extent of contact is regulated. We will combine high-content screening tools alongside in depth biochemical characterization to map new yeast contact sites, such as that between mitochondria and the nucleus, uncover the molecular tethers for contact where this is unknown and study the regulation of contact expansion and retraction. We will also create new systematic tools, such as new yeast libraries and High throughput Electron Microscopy (EM) approaches, to study contact sites and their proteomes. By answering these questions we hope to shed light on the diversity of cellular contact sites and their regulatory interplay that allows the cell to function as one coherent living unit through the changing requirements of life.