Endocytic and phagocytic pathways introduce huge amounts of material into cells that are ultimately degraded within the lysosome. Cholesterol derived from internalized material, is transported from the lysosome to the ER. This delivery of cholesterol to the ER is a critical step in maintaining cholesterol homeostasis. 

We have shown that the lysosome and the ER form transient connections where the membranes of the two organelles are physically associated.  These connections, known as membrane contact sites, allow exchange of material and protein-protein interactions between the two organelles.  We are trying to identify the proteins involved in regulating these contact sites and to understand the relationship between lipid transport and the ER-lysosome interface.

Defects in lipid transport result in lipid accumulation in lysosomes that is associated with several neurodegenerative diseases, including a rare but devastating childhood lysosomal storage disease, Niemann Pick type-C (NPC). Lipid accumulation is also believed to be a major contributing factor to the development of Age-related Macular Degeneration (AMD), the most common cause of vision loss in the elderly. 

By learning more about the regulation of ER-lysosome contact sites and their role in lipid transport, we aim to identify tools with which to mobilise lipids from the lysosome to alleviate lysosomal storage defects in diseases such as NPC and AMD.