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SCHOOL OFFISHA NEW DIRECTION INPARKINSON’S RESEARCHBY JUSTIN HOPPERCAPTION T/KK. LOTHROPEdward Burton, an MD, looksforward to the day when the twosides of his work coalesce. As apracticing clinician in UPMC’s Departmentof Neurology, Burton spends a few dayseach week seeing patients suffering fromParkinson’s and other neurodegenerative diseases.As a research scientist in the University’sPittsburgh Institute for NeurodegenerativeDiseases (PIND) and assistant professor ofneurology and of microbiology and moleculargenetics, Burton spends the balance of histime with an unlikely subject—zebra fish.Unlikely, that is, for a practicing MD.Besides being home-aquarium favorites, zebrafish have long been found in labs studyingdevelopmental biology. In the early days of theirlives, zebra fish are transparent—a state madepermanent in the human-engineered speciescalled Casper zebra fish. This gives researchersthe opportunity to view physiological changesin a living, growing vertebrate. But in 2004,Burton looked at Pitt’s world-class zebra fishfacilities—aquarium tanks stacked 10 feet highfilling a football-field-sized room—and beganto think, “What could these animals tell usabout Parkinson’s disease?”“You can do things with zebra fish youcan’t do with other animals,” says Burton.“If we had a zebra fish model for Parkinson’s,because they’re transparent we could look atthe biochemistry [of the disease and potentialCOURTESY E. BURTONtreatments] in a living animal.”Before zebra fish can be effectively usedto study Parkinson’s, someone needs to createa model—to understand how the diseaseaffects a zebra fish’s behavior and biochemistryin ways that can be correlated with the sameeffects in a human. (Since 2004, several otherlabs around the world have begun working oncreating this model, often using Burton’s publicationsas groundwork.)Behavior is relatively easy: Zebra fi share active critters with fast-paced lives, andBurton can tell a Parkinsonian fish withintwo hours (that makes it possible to do quick,large-sample tests for drug effectiveness). Infact, Burton and others at PIND showed thatscientists could make a zebra fish observablyParkinsonian by knocking out its dopaminesystem.The biochemistry is tougher to sort out buthas come a long way recently, as evidencedby a paper Burton and colleagues publishedlate in 2011 in The Journal of BiologicalChemistry titled “Hypokinesia and ReducedDopamine Levels in Zebrafish Lacking -and 1-Synucleins.” This research has madean important advance towards establishingA 7-day-old zebra fish larva used to studyneurodegenerative disease swims in the wellof a plate in Burton’s laboratory.Burton’s zebra fish model for Parkinson’s bymapping zebra fish synucleins—proteins presentin neural tissue that are heavily implicatedin Parkinson’s research.“Synucleins are important in Parkinson’s.For example, rats lacking -synuclein becomeresistant to toxins commonly used to modelParkinson’s,” says Burton. “We wanted toknow, ‘Do zebra fish have -synuclein?’”The answer, it turned out, was no. Whichmakes it somewhat more complicated, but byno means impossible, to create the model. Hislab will attempt to genetically engineer a fishwith -synuclein.That fish is next on Burton’s to-do list. Hebelieves there will be a big payoff in terms ofthe ability of scientists to witness Parkinsonianbiochemistry and degeneration in a transparentmodel. “It’s a long road, because we’vegot to invent everything ourselves [in termsof techniques and reagents],” says Burton.“Creating an effective treatment for humanpatients is a multidecade process.” ■10 PITTMED