Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

Our knowledge of the functions for membrane contact sites within cells is extremely limited yet they are present in all eukaryotic cells, from budding yeast to humans. Hence employing models such as the budding yeast to make breakthrough fundamental discoveries will lead to a better understanding of membrane contact site function in humans and their roles in disease. A major contributing organelle to membrane contact sites is the endoplasmic reticulum, which makes contacts with all other organelles in the cell. Some well characterized contacts are with mitochondria, plasma membrane, lysosomes, peroxisomes, Golgi and endosomes. However, membrane contact sites are not restricted to the endoplasmic reticulum and have been observed between mitochondria and plasma membrane and vacuoles/lysosomes. Main functions ascribed to membrane contact sites so far are in lipid and calcium traffic, cell signaling, and organelle biogenesis/homeostasis. The work proposed in this grant will use yeast to identify new components of membrane contact sites and define their functions and organization in much more detail. This will be through the use of high- resolution microscopy, genetic and biochemical approaches. The importance of membrane contact sites in human disease is also being uncovered through defining proteins with functions at membrane contact sites and include cancer, obesity, diabetes, and neurological diseases. However, many of the disease mechanisms have yet to be defined largely due to a lack of a clear understanding of the physiological functions of MCSs. This work will expand our understanding of these mechanisms