Cellular growth and integrity require membrane growth and integrity. We are using cross-disciplinary approaches to elucidate vital roles of inter-organelle contacts in membrane biogenesis and homeostasis at the molecular, ultra-structural, cellular, and tissue levels. Inter-organelle contacts serve as key sites for the coordinated regulation of membrane lipid metabolism and transport. Our studies have focused on contacts between the endoplasmic reticulum and the plasma membrane (ER-PM contacts), providing new understanding of membrane lipid and calcium dynamics during regulated exocytosis and polarised secretion. We are currently examining ER-PM contact architecture and function in hepatocytes, polarised epithelial cells of the liver. These investigations are suggesting new strategies to control biliary secretion that may prove beneficial in the treatment of liver disease.
Furthermore, we are probing how alterations in inter-organelle contacts and membrane lipid homeostasis result in organelle damage. These studies are revealing novel protective pathways that sense and respond to membrane stress conditions to ensure membrane integrity and organelle homeostasis. Numerous diseases are caused by imbalances in membrane lipid homeostasis including cancer, diabetes, and neurodegenerative disorders. We expect our investigations will identify new targets and strategies for the treatment of diseases caused by disruptions in membrane lipid and organelle homeostasis.
Medical Research Council
Ioanna Sevastou (Research Fellow)
Gary Chung (Research Fellow)
Ffion Thomas (PhD Student)
Bailey Hewlett (PhD Student)