Grant: Operating Grant

The goal of this research proposal is to define the contribution that the endoplasmic reticulum (ER) makes to the establishment of cell polarity and in the control of cell growth. Cell polarity is the spatial separation of cell function and it ensures that each daughter cell contains a complete copy of the genetic material along with the necessary cellular components to enable successful future cell divisions. Cell polarity is therefore a critical factor underlying many types of cancer, because aberrant cell polarization can result in faulty segregation of the genetic material leading to uncontrolled cell growth and tumour formation. Successful sexual reproduction also relies on cell polarity as it is critical to the processes of meiosis and gametogenesis, which in humans is the creation of sperm and egg cells, each carrying a single copy of all 23 chromosomes. When polarity fails in these circumstances and sperm or eggs receive too few or too many copies of a chromosome, devastating conditions such as Edward syndrome (1 in 6,000 births), Down Syndrome (1/8,000) and Patau syndrome (1/10,000) result. More than 90% of Edward and Patau syndrome babies die before the end of their first year. Cell polarity is also responsible for cell shape, which enables functional specialization and creation of specialized cell types such as neurons, epithelial cells and migrating blood cells. Without these specializations, multicellularity and the complexity of multicellular organisms could not exist. The ER is the largest internal membrane system in the cell that primarily functions in lipid and protein synthesis, and calcium storage, and plays roles in diseases such as obesity and type II diabetes. We have discovered the genes that create polarization of the ER and the aim of this grant is to uncover the physiological processes regulated by ER polarization and how this affects cell polarity, with the hope of applying these findings to human disease.