Justin Hayase MSTAR Presentation Guo Lab July 23,2009 Parkinson’s Disease: A genetic screen to investigate the Pink1/Parkin pathway in Drosophila Justin Hayase MSTAR Presentation Guo Lab July 23,2009

Parkinson’s Disease Degeneration of the substantia nigra Resting tremor, bradykinesia, rigidity, postural instability 1-2% of the population 95% sporadic, 5% familial Major treatment is dopamine replacement

Familial Parkinson’s Pink1 Parkin Pink1 – PTEN induced kinase 1 Parkin – E3 ligase α-synuclein LRRK-2 DJ-1 ATP13A2 Pink1 Parkin

How can flies be used to study Parkinson’s Disease?

Pink1 Mutant Flies Male sterility Mitochondrial defects Muscle degeneration Dopaminergic neuronal degeneration Increased sensitivity to ROS Functional conservation between humans and flies Ira E. Clark, et al. Nature 441, 1162-1166(29 June 2006)

What are other players in the Pink1/Parkin pathway?

Materials and Methods Unbiased genetic screen ~200 RNAi lines from the Laski lab Crossed to 705f (Pink1 mutant) Characterization of the indirect flight muscle Mitochondrial morphology

Results

Conclusions This is just the beginning! Identification of ~6 genes for further investigation Mitochondrial role in neurodegenerative processes – not just the substantia nigra!

Acknowledgements Dr. Ming Guo Lok Leung The Guo Lab Thank you!