The lysosome is a key organelle that is essential for quality control via the degradation of other organelles and proteins as part of the process of autophagy. In this project, we will investigate the functional relationships of three proteins, CLN2, CLN3 and CLN5, implicated in autophagy and/or lysosomal function by virtue of mutations in those proteins causing similar lysosomal storage disorders characterized by lysosomal accumulation of subunit C of mitochondrial ATP synthase. A variety of molecular and cell biology methods will be employed both in vitro using cell culture and yeast, and in vivo using zebrafish, including recently developed CRISPR technology.
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Mahmood F, Fu S, Cooke J, Wilson SW, Cooper JD, Russell C (2013) A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1 and displays progressive neurodegeneration accompanied by a reduction in proliferation. Brain 136:1488-1
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