Super-resolution microscopy probes for neurodegenerative disorders

There are an increasing number of diseases recognised as being related to the misfolding and aggregation of proteins. The most common of these are neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. There is currently a lack of techniques for studying protein aggregates, particularly in human samples such as cerebrospinal fluid. This has limited the availability of biomarkers required for early diagnosis. 

The major aim of this project will be to develop an optical sensing technology to characterise the protein aggregates in their native environment at the nanoscale. We have made use of a computational method to rationally design peptides that are able to bind to linear sequences of the aggregating proteins involved in Alzheimer’s and Parkinson’s disease. With Marc Vendrell (http://www.dynafluors.co.uk), you will synthesise these peptides and modify them through the addition of activatable fluorophores. In its unbound state, free rotation of the fluorophore leads to quenching whereas, upon binding to aggregates, the fluorophores rapidly become fluorescent enabling real-time imaging and kinetic studies. In the Edinburgh Single-Molecule Biophysics Group, you will use these peptides with state-of-the-art super-resolution microscopy methods to characterise protein aggregates in vitro, in patient-derived cells, and eventually in human samples.

Skills developed during the course of this project:
  • Synthetic organic chemistry. 
  • Single-molecule and super-resolution microscopy. 
  • An understanding of neuroscience and neurodegenerative disorders.
This is an interdisciplinary project. As all of the required training will be provided during its course, it doesn't matter what background you are coming from. If you'd like to find out more, please contact me and I'd be happy to arrange a chat.