Dr Sylvie Callegari awarded David Syme Research Prize
Dr Sylvie Callegari, a laboratory head at the Walter and Eliza Hall Institute of Medical Research (WEHI) and the University of Melbourne's Department of Medical Biology, has been awarded the David Syme Research Prize for her work titled Activating PINK1 to treat Parkinson's disease.
The University of Melbourne's David Syme Research Prize, nominated by the Faculty of Science, is one of Australia's oldest science awards, established in 1906 to recognise the best original research in biology, physics, chemistry or geology produced in Australia during the previous two years.
For almost two decades, scientists have known that mutations in the protein PINK1 can cause early-onset Parkinson's disease. PINK1 acts as a molecular beacon that identifies damaged mitochondria – the cell's energy-producing structures – and signals for their removal.
"For nearly 20 years, no one had been able to see what human PINK1 actually looks like, or how it attaches to damaged mitochondria.” Dr Callegari said.
Using advanced cryo-electron microscopy and innovative biochemical approaches, Dr Callegari and her collaborators captured the first high-resolution images of human PINK1 bound to the surface of mitochondria.
The breakthrough revealed how PINK1 recognises damaged mitochondria and uncovered an unexpectedly complex molecular arrangement on the mitochondrial surface involving the mitochondrial transport machinery and a protein known as VDAC2. The findings also explain how disease-causing mutations disrupt PINK1 function and contribute to Parkinson's disease.
This research represents a major advance for both Parkinson's disease research and fundamental mitochondrial biology. In addition to providing the first structure of human PINK1, the work delivered the first structure of human VDAC2 and reveals new insights into how proteins enter mitochondria to produce the energy to keep us alive.
“Being able to see PINK1 opens the door to developing new ways to boost PINK1 to improve mitochondrial clean-up and halt the progression of Parkinson’s disease,” Dr Callegari said.
Dr Callegari is honoured to receive the award and join the illustrious names that have won it before her.
“This is a valuable recognition of our work on PINK1 and, having just started my own lab, it is a strong encouragement that my research is heading in the right direction.”
Dr Callegari’s findings have also attracted interest from pharmaceutical companies.
A committee from the University of Melbourne's Faculty of Science selects the David Syme Research Prize winner each year.