1. 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

2. 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

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

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

5. 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, (29 June 2006)

6. What are other players in the Pink1/Parkin pathway?

7. 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

8. Results

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

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