Harnessing Optogenetics and Nanoprobes to Modulate & Monitor Membrane Tension
Project ID: 2531ad1545
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Research Theme: Physical Sciences
UCL Lead department: Laboratory for Molecular Cell Biology (LMCB)
Lead Supervisor: Christopher Stefan
Project Summary:
Migrating cells, including metastatic cancer cells, are constantly exposed to mechanical forces resulting in rapid alterations in plasma membrane (PM) tension. This project will use inter-disciplinary approaches to address how cells sense and respond to changes in membrane tension and develop innovative strategies to target membrane stress in cancer cells.
The PM must withstand rapid increases in tension upon exposure to mechanical forces, and disruptions in PM integrity are linked to numerous diseases and disorders. Consequently, cells have evolved robust systems to sense and respond to PM stress by adjusting the composition and biophysical properties of the PM bilayer.
Yet when considering cell mechanics, tension within the membrane bilayer is often overlooked. This is because methods to monitor membrane stress (stretch) are limiting. This project will address how cells sense and respond to membrane stress using optogenetics and novel membrane nanoprobes to modulate and monitor membrane tension.
The Stefan lab is uncovering unprecedented roles of contacts between the endoplasmic reticulum and plasma membrane, ER-PM contacts, as well as phosphoinositide (PI) kinase and target of rapamycin complex 2 (TORC2) signalling cascades in the control of PM tension, homeostasis, and integrity.
This PhD research project aims to determine: 1) how ER-PM crosstalk and PI kinase-TORC2 signalling pathways modulate PM tension, 2) how alterations in these pathways impact PM organisation and integrity using advanced nanoprobes and optical approaches, and 3) how modulating membrane tension impacts cell migration and integrity.
The project will employ state-of-the-art imaging approaches (super resolution microscopy, FRET, FRAP, FLIM, CLEM), as well as biochemical, biophysical, structural, and computational approaches to study membrane mechanotransduction.
We expect to uncover fundamentally important regulatory mechanisms for membrane homeostasis, to develop new technologies to modulate and monitor membrane tension, and to uncover new strategies to target membrane tension in cancer cells.