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Paul J. Lockhart, Ph.D.

Armed with new techniques, researchers can now “mine” databases containing the genetic sequences of thousands of people, to find genes that cause various diseases. Australian researcher Paul J. Lockhart, Ph.D., a scientist whose work has been previously supported by PDF, is a leader among these “genetic prospectors.”

Dr. Lockhart seeks out Parkinson's disease (PD) genes among the records of the Victoria Clinical Genetics Service, a part of the Murdoch Childrens Research Institute (MCRI). At MCRI, Dr. Lockhart serves as co-director of the Bruce Lefroy Centre for Genetic Health Research and as head of the Neurogenetic Research Laboratory. Over the past two years, he and his colleagues have discovered five genes that are linked to neurodegenerative and other disorders. One of the five, currently known simply as “gene X,” is believed to underlie some cases of Parkinson’s.

Dr. Lockhart got his start in PD genetics halfway around the world, at the Mayo Clinic in Jacksonville, FL. That’s where, in 2000, he began his postdoctoral research to identify and study novel genes that cause PD, such as UCHL1. Through its International Research Grants Program, PDF supported a portion of Dr. Lockhart’s work in 2003-04. The program helps promising young researchers to pursue innovative ideas, and acquire the results they need to win larger grants. Dr. Lockhart’s studies were carried out in the laboratory of John Hardy, Ph.D., and Matthew Farrer, Ph.D. (Dr. Farrer’s work has also been supported by PDF and readers can refer to the Winter 2012 edition of News & Review to read an article he authored on genetics and PD.)

“The PDF funding was instrumental in enabling me to continue working in the PD field when I returned to Australia,” says Dr. Lockhart. He adds that it was not only the science, but also the collaborations forged during his postdoctoral years, that helped him to start up his own laboratory at MCRI in 2004, and go on to receive a Career Development Fellowship from the Australian National Health and Medical Research Council.

PDF’s early support of Dr. Lockhart helped to set him on the path to more recent results. “This field of study has remained a passion for me,” he says. Gene X underlies some of those rare cases in which PD is inherited. In the family he studied, three men were affected by earlyonset disease. To find this gene, he used new data-mining technologies, which make it possible to pinpoint inherited genetic mutations in families where only a few members are affected.

With this success came the opportunity to once again work with PDF. This year, PDF is supporting the next phase of his work on gene X. First he will investigate how often the gene is mutated in people with Parkinson’s. “In addition, little is currently known regarding the function of the protein that is encoded by the gene,” says Dr. Lockhart. “Our research will determine the role of the protein in neurons and help to determine why the brain cells we call dopaminergic neurons are lost in PD.”

The results may help scientists begin to understand why people with PD have different motor and nonmotor symptoms, and why disease progression varies so much among people with PD. “Ultimately,” says Dr. Lockhart, “this study will contribute to the identification of new treatments and therapies.”

Dr. Lockhart’s research is funded through the International Research Grants Program. In FY2013, the budget for this program will be $1.16 million.