Characterisation of the functional role of the Batten disease gene, cln3, in Drosophila. (360G-Wellcome-082004_Z_07_Z)

Batten disease/NCL is an inherited neurodegenerative disease of childhood characterised by the accumulation of abnormal autofluorescent material within lysosomes. The most common form, Juvenile NCL, is caused by mutations in the Cln3 gene. A role in endosomal/lysosomal function has been suggested in non-neuronal cells but it is uncertain if Cln3 plays the same function in neurons. We aim to increase our understanding of Cln3 function by investigating its role in Drosophila. Our preliminary work has revealed that Drosophila Cln3 shares many features with the human protein. Our data and that of others suggests a role for Cln3 in membrane trafficking. We will utilise our experience in study of the Drosophila nervous system to investigate (i) the cell biology of Cln3 both in vivo and in vitro, (ii) the functional requirement for Cln3 and the pathological role of modified Cln3 proteins and (iii) partner proteins that function with Cln3 within the nervous system. We hope to establish the pr ecise compartment within the neuron where Cln3 is expressed and identify the functional pathway in which it acts. Additionally we will follow and characterise the pathology that occurs when the protein is absent or non-functional and characterise the cells that require Cln3.