Harnessing DNA Nanoprobes to Monitor and Modulate Membrane Tension
Project ID: 2228cd1336 (You will need this ID for your application)
Research Theme: Physical Sciences
UCL Lead department: Lab for Molecular Cell Bio
Lead Supervisor: Christopher Stefan
Project Summary:
Cells are constantly exposed to intrinsic and extrinsic mechanical forces that can result in rapid alterations in plasma membrane tension. Consequently, cells must have robust systems to adjust the composition and biophysical properties (tension, lipid packing order, asymmetry, fluidity, permeability, and thickness) of their plasma membrane.
Disruptions in plasma membrane integrity are linked to numerous diseases and disorders. Yet when considering membrane mechanics, the cytoskeleton and the actomyosin cortex are primarily studied, while 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 novel fluorescent DNA nanoprobes.
The Stefan lab is uncovering novel roles of contacts between the endoplasmic reticulum and plasma membrane, ER-PM contacts, in essential PM homeostasis pathways including phosphoinositide (PI) kinase and target of rapamycin complex 2 (TORC2) signalling cascades.
The project will be in collaboration with the Howorka lab (UCL Chemistry) who are developing new DNA nanoprobes to modulate and measure the biophysical properties (including tension and mechanical stress) of membrane bilayers.
The student will determine i) how ER-PM crosstalk and PI kinase-TORC2 signalling modulate PM tension, ii) how alterations in these pathways impact PM integrity, and iii) develop next-generation fluorescent DNA nanoprobes to monitor membrane bilayer tension.
The project will employ state-of-the-art imaging approaches (super resolution microscopy, FRET, FLIM), biophysical approaches (optical and magnetic tweezers, AFM) in collaboration with Dr. Nicholas Bell (UCL LMCB and Physics), as well as computational approaches to model membrane tension.
We expect to uncover fundamentally important regulatory mechanisms for membrane homeostasis and to develop new technologies and applications relevant to health and disease.