Monitoring molecular mobility in the intact brain with anisotropy-FLIM

Project ID: 2228cd1442 (You will need this ID for your application)

UCL Lead department: Queen Square Institute of Neurology

Project Summary:

Neural activity in the brain relies on rapid movement of signalling molecules, outside and inside nerve cells. The knowledge of molecular diffusivity on this small scale is crucial: (i) it should establish critical constraints for the dynamics of molecular reactions and ionic currents that shape neural activity; (ii) it could provide a potentially critical readout of local physiological and pathological changes undetected by other means; (iii) it should help to discern intra- versus extracellular components in diffusion-weighted MRI protocols in humans. Built on our in-house established methods, such as FLIM and time-resolved fluorescence anisotropy imaging (TR-FAIM) in brain slices, the research program aims to expand them to the intact brain. This will enable the monitoring of molecular diffusion on the nanoscale in live animals (rodents), using either water-soluble small-molecule fluorophores or fluorescent molecular motors (BODIPY-type) that could be genetically encoded for cell-targeted expression. Our ultimate objective is to establish causal associations between micro-viscosity of the specific extracellular or intracellular environments and target-cell physiology or pathology that may affect functional traits of the respective neural circuits. The host group comprises experts in single-cell electrophysiology, time-resolved and multiplexed fluorescence imaging, two-photon microscopy, optics, cellular and neural-networks biophysics, molecular biology. We are equipped with several cutting-edge two-photon excitation-uncaging imaging systems coupled with patch-clamp physiology, and all the related infrastructure support. The host department provides world-leading academic environment. An ideal candidate will have a background in neuroscience, physics / biophysics, cell imaging, and/or FLIM methods, and show enthusiasm for implementing cutting-edge physics methods in brain research. The research project will be tailored to the candidate’s skills and involve focusing on either neuroscience or biophysical (imaging) aspects of the program.