3D super-resolved measurement of molecular dynamics in the cell membrane

Super-resolution microscopy techniques are now routine for imaging of live and fixed cells with high spatial resolution. However, many of these techniques capture images very slowly, and they lack the high speed needed to explore and quantify cellular dynamics at time scales required to measure important processes such as molecular diffusion. Fluorescence correlation spectroscopy (FCS) is one technique that enables the study of these fast processes, but the spatial resolution of FCS is limited by the optics used.

Membrane trafficking in living cells involves a range of motions, from the study of vesicle movement within the cell (including vesicle diffusion, capture and tethering events) to the study of the dynamics of individual molecules within a membrane compartment (e.g. transporters and receptors in the plasma membrane).  

This project will make use of a new STED – FCS - FLIM microscope recently purchased by the University of Strathclyde as part of a BBSRC ALERT award to explore fast molecular diffusion. However, rather than applying the recently proven combination of stimulated emission depletion (STED) and FCS techniques, we will here explore a totally new method to achieve this aim, which provides inherent global 3D FCS measurements at speeds limited only by the detector electronics. Successful implementation will provide new insights into molecular dynamics in cell membranes. This project will use fat cells as a paradigm. Insulin-regulated membrane trafficking is a vital facet of fat cell biology and is known to be impaired in diseases such as Type-2 diabetes. This project offers the potential to reveal new paradigms relevant to healthy cells and disease processes.

Applicants should have a degree in Physics, Chemistry, Bioscience, Biophysics or similar and should be motivated to explore new research questions and directions. Some previous experience in microscopy, photo-physics, optical instrumentation or fluorescence spectroscopy is desirable but not required. The project will combine experimental measurements, methods development and advanced data analysis, as well as the preparation of live cell specimens.

The project is anticipated to start in Autumn 2022, but an earlier start may be possible. Full funding (stipend at EPSRC rate and fees) is in place for UK applicants only.

For informal enquiries, please contact Gail McConnell, Group Leader of the Centre for Biophotonics: [Email Address Removed].