Lysosome turnover in health, ageing and disease

Damaged cellular components and material taken up from outside the cell can be digested in lysosomes. Accumulation of undigested material occurs in many age-related neurodegenerative diseases such as Alzheimer’s disease and age-related macular degeneration (AMD). Research aimed at improving cells’ degradative ability has led to the identification of promoters of synthesis of new lysosome constituents. It is unclear how these are packaged into new lysosomes and how old and damaged ones are removed. Retinal pigment epithelial (RPE) cells engulf and degrade damaged photoreceptor fragments and RPE lysosome dysfunction has been implicated in early AMD. 

We aim to determine how new lysosomes are formed and how old or damaged lysosomes are cleared. We will develop a molecular signature of old or damaged lysosomes in cultured RPE and test its efficacy in identifying dysfunctional lysosomes in ageing and diseased retinae.

Our findings will aid development of therapies for neurodegenerative diseases.