Endoplasmic Reticulum Transport and Morphoregulation in Neuron (Patho) Physiology

Summary

The Endoplasmic Reticulum (ER) is a multifunctional organelle, shaped as a contiguous network of membranous pipes extending throughout the cell periphery. Its morphology benefits intercellular communication, allowing controlled distribution of ER luminal solutes (e.g. Ca2+ in muscular/neuronal signalling) and membrane-bound components to distant sites and adjoining organelles.

Mounting data points to a critical role of ER morphology regulation in neuronal functioning. This is prominently exemplified by the direct association of ER morphogens (aka ER shaping proteins) with neuropathologies such as Hereditary Spastic Paraplegia and dementia-related diseases.

Project aims

We seek understanding of how ER’s network integrity, morphological regulation and luminal transport support neuronal cell functioning, with a view to identifying new intervention targets for prevention of neurodegenerative avalanche.

The projects on this theme involve editing of candidate genes in cells with potential to differentiate to neurons/glia, and analysing the consequences of the targeted mutagenesis on structure/function of neuronal ER using live cell microscopy techniques such as super-resolution imaging and single-particle tracking and neuronal activity analyses e.g. calcium imaging (carried out in collaboration with optics physicists and computer scientists). Focused projects exploring benefits of modulation (e.g. induced degradation) of candidate ER-morphogens for neuronal health and axonal regeneration are also available.  

Contact details

Edward Avezov (ea347@medschl.cam.ac.uk) – UK Dementia Research Institute  

Opportunities

This project is open to applicants who want to do a:

• PhD
• MPhil