The glucosylceramide-depletion hypothesis for neurodegenerative disease: Role of lysosomal cations and membrane contact sites

We have preliminary evidence that neurodegenerative diseases have a deficit in a particular type of biological molecule, a glucolipid. We have previously shown that glucolipid outside the lysosome leads to defective recycling inside lysosomes. The project will address a new hypothesis for how the lysosomes and mitochondria are not functioning correctly. We have identified new targets that increase glucolipids and help the lysosome work better in neurodegenerative disease. Using both external and internal collaborators the proposed studentship would use fly and cell culture models of disease to investigate the role of membrane contact sites in lysosomal cation gradients (Emily Eden UCL). Using fluorescent activity-based probes (Hans Aerts, Leiden) the localisation of GBAs in healthy and diseased cells as well as the effect of GBA inhibition on glycolipid levels and saturation using in house LC-MS.

Enquiries

Potential applicants can contact Dr Dan Sillence, for any questions about the project or for informal enquiries (dsillence@dmu.ac.uk).

Applicants must:

• Possess a UK Honours degree with at least an upper second class, or overseas equivalent degree, or a relevant Masters qualification.
• Demonstrate competence in the use of the English language. Please see section 5b here for further details on meeting our English language entry criteria.

The deadline to apply is Monday 8^th July 2024.

Information on how to apply for this scholarship please visit https://www.dmu.ac.uk/doctoral-college/study/scholarships.aspx