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Custom-made treatments designed for your DNA

This research has immediate applications for studying neurodevelopmental and neurodegenerative diseases. The two teams led by Associate Professor Yang and Assistant Professor Sun are particularly interested in using it to study new treatments for Parkinson’s disease that can be customised according to a patient’s unique genetic makeup.

Parkinson’s disease is associated with the loss of dopamine-sensitive neurons in the midbrain – a cell type that can be modelled using membrane organoids.

“We all have different DNA, so each patient will have a different experience with their condition, and a different response to treatments. A one-size-fits-all approach doesn’t work,” said Associate Professor Yang.

This is where organoids present a unique opportunity for real breakthroughs. By taking a sample of a patient’s skin cells – a quick and non-invasive procedure – scientists turn these cells back into stem cells, which are then grown into a brain organoid that contains the patient’s own DNA.

“Ultimately, we’re working to make these models more accurate so we can use them as powerful tools to discover new medications for Parkinson’s disease, tailored to and tested on a model of each patient’s unique brain cells.”

International collaboration: multiplying strengths

The partnership with Singapore was a natural fit, said Associate Professor Yang, thanks to Duke-NUS’s world-leading expertise in stem cell and developmental biology, and access to state-of-the-art research facilities that complement the facilities at Sydney. The research is supported by an Ignition Grant from the University of Sydney’s Office of Global and Research Engagement.

“We happen to share a common interest in stem cells and use them as a model to study disease. Our complementary expertise made this collaboration a natural choice,” Associate Professor Yang explained. “The Ignition Grant was instrumental to making this research a reality, thanks to the funding for research expenses and visits to each other’s facilities so we can collaborate in-person. It also opened up organisational support to help us navigate the complexity of international partnerships and regulations.”

Assistant Professor Alfred Sun from Duke-NUS Medical School said: “Pengyi and his team bring expertise in computational biology and data integration, areas that perfectly complement our strengths in stem cell and developmental neuroscience. By combining these capabilities, we can bridge the gap between complex molecular data and biological function, accelerating the translation of stem cell research into clinical application.”

From sci-fi to reality

With further funding applications pending, the Sydney-Singapore partnership is poised to expand its research into modelling a range of neurodegenerative diseases using patient-derived organoids and developing new computational models to guide organoid differentiation.

“���帣��Ƭ in Science Advances showed that we can still refine our organoid models further, and provided useful insights into how we can make this happen,” Associate Professor Yang said.

Armed with this information, the team plans to create improved midbrain organoids which they will use to study  neurodegenerative diseases, find drugs that could help treat them, and test their potential for cell therapy and regenerative medicine.

“This research collaboration demonstrates the incredible potential of combining cutting-edge biology with advanced machine-learning capabilities. This was once science-fiction – creating a mini organ in a lab and using it to discover and design bespoke medical treatments. We’re making it a reality.”