Project Cell signaling in progerin-expressing endothelial cells Program Engineering Term Academic Year 2025 Status Accepted Research Area vascular biomechanics, mechanotransduction, cell and molecular biology Description A mutant truncated form of lamin called progerin is responsible for premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Interestingly, progerin is also found in normal adults, and increases with age. Defective nuclear lamina in aged cells share similarities with nuclei of HGPS cells such as distorted nuclear shape and increased mechano-sensitivity. HGPS patients share something else with older people: the progression of cardiovascular diseases such as atherosclerosis. Endothelial cells in the vasculature are constantly exposed to hemodynamic forces of blood flow on the lumen side. The presence of progerin yielded stiff nucleus, but softer chromatin in nuclear interior, which probably contributed to decreased responsiveness to mechanical stress. In this project, we will develop an endothelial cell line that stably express GFP-fused wildtype lamin and progerin proteins. These cells will be used in flow experiments to examine the effect of shear stress on how progerin affect signaling transduction such as the AMPK pathway, and the subsequent effect on cell homeostasis and aging. Supervisor Julie Ying Hui Ji Mentor Type of work required Students will be involved in a range of techniques, such as cell culture, transfection, fluorescence live cell imaging, immunohistochemistry, quantitative image analysis, Western blotting, PCR. Websites Qualifications At least 3.0 GPA. Knowledge of cell culture is recommended, but not required. Credit Hours 0 Weekly Hours 10 (estimated)