The in situ molecular structure of active calcium ion channels

In the mammalian nervous system, specialized subcellular structures including synapses mediate learning and memory. The focal release of Ca2+ ions by ion channels is thought to be the signal that drives local, long-lasting structural remodeling within synapses. We are seeking a highly motived PhD candidate to investigate the structural mechanism of these fundamental cellular processes.

This interdisciplinary project involves exploiting recently developed mouse genetic reagents to determine the in situ 3D molecular structure of calcium ion channels and to investigate activity-dependent synaptic remodelling.The methods used will include: i) Electron tomography and computational image processing. ii) Cryogenic correlated light-electron microscopy (cryoCLEM) of synapses and thin vitreous sections. iii) Biochemical and genetic labelling of synaptic proteins. Applicants from all backgrounds in natural or physical sciences are encouraged to apply. Some experience with programming (e.g. Python, Matlab or similar) will be highly advantageous.

The University of Leeds has invested £10m in two 300 keV Titan Krios electron microscopes, a high-pressure freezer, and cryogenic light microscope. Thereby, the successful applicant will receive a training at the cutting edge of structural biology and molecular neuroscience.