Programme 9: Biophysical, Biochemical and Cellular Characterisation of Amyloidogenic Protein Interactions with PrPC and their Subsequent Toxicity

Background

Despite the diversity of clinical symptoms associated with different protein misfolding diseases such as Alzheimer’s disease and Creutzfeld-Jakob disease, similarities in their mechanisms suggest that distinct pathologies may interact at the molecular level.

Rotation Project

This rotation project builds on our group’s extensive experience in studying the Aβ-PrPC complex, and expands this to address whether PrP interacts with any other disease-associated proteins e.g. proteins associated with Parkinson’s disease, Type 2 diabetes and tauopathies.  A broad range of established biophysical and biochemical techniques will be used to study the interaction of disease-associated proteins to PrP.

PhD project

This project will expand upon the work undertaken in the rotation project to pursue both structural characterisation of protein-protein complexes with PrPC and to establish whether PrPC binding is involved in the activation of toxic signalling cascades in cell lines and primary neuronal cultures. It will give the student an excellent knowledge of a wide-range of biophysical, biochemical and cellular techniques, including dynamic light scattering, amyloid detection assays and super-resolution microscopy. This project will involve collaborations both within the Unit and with external collaborators.