Bio 363 Human Genetics, Spring 2013
Parkinson's study sheet
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Background web reading
What are the symptoms?
What are some common treatments?
What part of the brain is most affected in Parkinson’s? How does that explain the symptoms? What is the role of dopamine?
How is the personalized genetic testing company 23andMe contributing to Parkinson's research?

Review basic biology of mitochondrial function in your intro biology textbook and/or other reliable sources.

Van Laar and Berman, 2012
What are the dynamic properties of mitochondria? How is that topic somewhat separate from bioenergetics?
What are a couple of the major proteins that mediate mitochondrial fission (division)?(Will help to keep track of these when you get to the main paper)
What are a couple of the major proteins that mediate mitochondrial fusion?
What are a couple of the major proteins that mediate mitochondrial transport?
What is mitophagy?
Do damaged mitochondria undergo proper mitochondrial fusion? Why or why not?
How does mitochondrial damage influence mitochondrial fission?
What is the apparent function of the fusion-fission cycle?
Why do neurons have special needs for mitochondrial dynamics?
What other neurodegenerative diseases have a connection with mitochondrial dynamics?
Some pesticides and other toxins are associated with Parkinson’s—what specific effects do these chemicals have on mitochondrial function?
Summarize how all the genes associated with Parkinson’s are connected with mitochondrial function.
Summarize how PINK1 and Parkin connect the phenomena of mitochondrial bioenergetics and mitochondrial dynamics (both fusion/fission AND transport).

Coune et al., 2012
Skim this paper for the main ideas.
What gene therapy approaches address symptomatic issues only?
What approaches target the progress of the disease without addressing the specific genetic defects themselves?
What approaches target the specific genetic defects themselves?
What approaches are most promising?
What are the challenges for implementing these approaches in humans?

Ziviani et al., 2010
In general, what groundbreaking advances did this paper and the others (in the extra folder) from 2010 report?
What organism and cell type are used in this study?
What is RNAi and how is it used in this study?
Fig 1: Does manipulation of PINK1 and Parkin levels affect mitochondrial shape?
Fig 2A and C: What do CCCP and paraquat do? What fluoresces green and red? What happens to Parkin when mitochondria are unhappy?
Fig 2B: What happens to mitochondria if exposed to CCCP for a long time? What gene products need to be present for that to happen to mitochondria?
Fig 3: This is a fun and complicated immunoprecipitation figure. Use the + and - to know what was in each set of transfected cells. Flag and HA are protein tags to which commercial antibodies are available. Ub is ubiquitin, a small protein that is added to proteins targeted for destruction. Where it just says WB, a western blot was done on the whole cell extract. Where it says IP and WB, only the complexes to which the IP antibody bound were then loaded on the gel for the Western blot. What do the results say about 1) which mitochondrial dynamics-related proteins get ubiquitinated, 2) which proteins must be present for that to occur, and 3) what proteins bind to what other proteins?
Fig 4: Look for what is necessary to get the higher (ubiquitinated) Mfn band in the anti-Flag Western blots. If you knock down PINK1 and add extra Parkin, do the bands come back? If you knock down Parkin and add back extra PINK1, do the bands come back? Do these results make sense with what PINK1 and Parkin do?
Fig 5: What is the big difference between A and B? How were samples obtained in B?
Fig 6: Where do we have to look for the control for this experiment?
What is the big picture for how mitochondrial dynamics seem to be related to Parkinson's disease? (Including conclusions from papers in the extra folder)