The role of glycosphingolipids in modulating membrane protein trafficking

The cell surface is decorated with a diverse array of proteins and lipids that mediate essential cell to cell contacts and trigger potent signalling pathways. An important class of lipids enriched at the cell surface are glycosphingolipids (GSLs). Imbalances in GSL levels underlie a range of severe disorders from neurodegeneration to cancer. I aim to define how altered GSL metabolism influences cell fate, driving disease pathogenesis. I have established that accumulation of GSLs leads to loss of proteins from the cell surface and identified this may be driven by direct interactions between GSLs and membrane proteins. 

Using multidisciplinary approaches, we will comprehensively establish which proteins are most sensitive to GSL imbalances, identify the mechanisms by which this occurs, and address how these changes influence disease pathways. 

This work will shed light on this understudied area of biology, providing a deep mechanistic understanding of GSLs in fundamental cellular pathways with clear medical relevance.