Neuronal Ceroid Lipofuscinosis (also known as Batten disease) is a group of inherited lysosomal storage disorders that affect infants and children. The disease leads to rapid neurodegeneration and death and there are no treatments or cures. Little is known about Batten disease but each form is caused by mutation in a specific gene controlling an enzyme or protein associated ultimately with lysosomal function. We have been investigating a form of the disease known as CLN6. This involves a mutation in the CLN6 gene that encodes a protein of unknown function. Our studies on cell and natural animal models, including a natural sheep model have shown that there are alterations in zinc transport in the brain during early stages of CLN6 Batten disease. Specially, expression of the zinc transporter, Zip7, is greatly altered in animal models of Batten disease and parallels changes in CLN6 protein. Additional studies have indicated that CLN6/Zip7 interactions may be critical for controlling autophagy and subsequently lysosomal function (as autophagy and the lysosome are closely associated). This project investigates how Zip7 controls autophagy in Batten disease through modulation of intracellular zinc homeostasis in neurons and glial cells in the brain.
The project will involve the culture of cell lines from animal models of Batten disease and examination of CLN6 animal tissues. Zip7 expression will be altered by knockdown or transfection of Zip7 constructs, and the effects on autophagy will be examined by microscopy and western blotting.
- PhD project but may also be considered for an Honours project.