Auckland Parkinson's research receives big US grants

Liggins Institute researchers will use a $226,000 grant from two major US-based foundations to investigate the genetics of Parkinson’s disease from an unusual and promising angle.

The funding comes from The Michael J Fox Foundation for Parkinson’s Research and The Silverstein Foundation for Parkinson’s With GBA.

The Michael J Fox Foundation, founded by the Canadian actor and writer of the same name, is the world’s largest non-profit funder of Parkinson’s research, and is dedicated to accelerating a cure for Parkinson’s disease and improved therapies for those living with the condition.

Mutations in the gene known as GBA – short for glucocerebrosidase beta acid – are the most common genetic risk factors for Parkinson’s, affecting about 10 percent of the more than six million people estimated to have the disease. The Silverstein Foundation is focused on cutting-edge research specifically for the treatment and prevention of Parkinson’s in GBA mutation carriers.

Associate Professor Justin O’Sullivan, a molecular scientist at the University of Auckland-based Institute, and his team will use a powerful 3D genome-mapping tool they devised to reveal the connections of GBA to other genes. They think parts of the gene may be acting as ‘DNA switches’ and disrupting the functioning of other genes that GBA comes into contact with through the way that DNA is coiled inside cells.  

We’re coming at it from a totally different angle – we’re looking into whether ‘switches’ inside GBA mutations turn up or down the functioning of other genes that they come into contact with. 

Associate Professor Justin O'Sullivan Liggins Institute

DNA, the long molecules containing our entire genetic blueprint, are around two metres long when unwound, but packed into cell nuclei measuring only 100th of a millimetre across. Through this coiling, segments that are far apart when the DNA is stretched out, come into contact with each other. 

Dr O’Sullivan and his team are at the forefront of international efforts to show that these spatial connections can change the functioning of genes and potentially play a role in a wide range of diseases.

“Most research into GBA’s role in Parkinson’s focuses on whether GBA mutations hamper the activity of a particular enzyme, a member of the cell’s ‘cleaning crew’ that degrades damaged or surplus cell parts,” Dr O’Sullivan says.

“We’re coming at it from a totally different angle – we’re looking into whether ‘switches’ inside GBA mutations turn up or down the functioning of other genes that they come into contact with. We think some of the more unusual findings about GBA might be able to be explained if it has connections to other genes.

“If we are right, we will identify a network of interrelated Parkinson’s genes. This may help advance research efforts for therapies, and bring together previously confusing or unrecognised connections.”

His team has already applied its unique 3D genome-mapping tool, which relies heavily on computational analysis, to illuminate a previously unknown genetic driver in type 1 diabetes, and help explain why clusters of certain diseases and characteristics often go hand-in-hand in the same person.

“For us, this grant is an amazing opportunity to investigate a disorder that has a huge impact on people. We hope to make insights that ultimately make a real difference to patients.”

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