Stefan Lab

The plasma membrane defines cellular identity and integrity. We are discovering vital roles of phosphoinositide signalling networks and inter-organelle communication in the control of plasma membrane domain organisation, homeostasis, and repair at the molecular, ultra-structural, cellular, and tissue levels.

Phosphoinositide Signalling and Inter-Organelle Crosstalk in Plasma Membrane Homeostasis and Repair: The plasma membrane must withstand rapid changes in tension upon exposure to mechanical forces and environmental stresses. We are utilising cross-disciplinary approaches (advanced imaging, biochemical, biophysical, structural, and computational) to determine how cells sense and respond to membrane stress and damage. These studies are revealing critical roles of phosphoinositide kinase signalling and non-vesicular membrane lipid trafficking pathways in plasma membrane homeostasis and repair upon alterations in membrane tension.

Phosphoinositide Signalling and Inter-Organelle Crosstalk in Epithelial Cell Architecture: We are uncovering unprecedented roles of phosphoinositide metabolism and inter-organelle communication in plasma domain organisation and function in hepatocytes, polarised epithelial cells of the liver. These studies are also revealing striking alterations in inter-organelle contacts and membrane organelle morphology as novel hallmarks of hepatocyte pathology in the progression of severe liver disease. We expect our investigations will identify new targets and strategies for the treatment of numerous diseases caused by disruptions in inter-organelle contacts and membrane homeostasis.

Principal funder

Selected publications

Gomes Castro et al. (2022). Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution. eLife. DOI: https://elifesciences.org/articles/74602

Chung et al. (2022). The ultrastructural organization of endoplasmic reticulum-plasma membrane contacts is conserved in epithelial cells. Mol Biol Cell. DOI: 10.1091/mbc.E21-11-0534-T

Thomas et al. (2022). Tricalbin proteins regulate plasma membrane phospholipid homeostasis. Life Sci Alliance. 5(8):e202201430. DOI: 10.26508/lsa.202201430

Omnus D, et al (2020). A Heat Sensitive Osh Protein Controls PI4P Polarity. BMC Biology. 18:28. DOI: 10.1186/s12915-020-0758-x

Collodo D, et al (2019). Tricalbins Control ER Curvature to Maintain PM Integrity. Developmental Cell. 18: 476-487.e7. DOI: 10.1016/j.molcel.2019.06.037

Nishimura T, et al (2019). Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis. Molecular Cell, 75: 1043-1057. DOI: 10.1016/j.molcel.2019.06.037