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Improve research capability or be left behind: chairman

Q&A: Rules on multiple grants
Biological and Chemical Sciences
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Stroke victims may eventually benefit from basic research at The Hong Kong University of Science and Technology into how proteins work in the brain.
  Signalling in the brain is mediated by a diversity of neurotransmitters, explained Principal Investigator Prof Mingjie Zhang. Binding to these neurotransmitters are receptors and ion-channels that are organised into multi-protein complexes by “scaffold” proteins.
Prof Zhang (above); structure of a PSD-95 “scaffold protein” with target sites for potential drugs indicated (left).

  Prof Zhang’s research is looking at the structural and biochemical basis of how scaffold proteins organise brain cell signalling complexes. He believes the research is important not only for understanding the signalling process in brain cells but could help provide leads for the development of drugs to treat neurodegenerative diseases such as stroke.
  The first research step was to determine the shape of the protein molecules involved in the scaffolds and understand why they perform specific functions in controlling how brain cells work. Using nuclear magnetic resonance spectrometers, researchers are able to survey individual atoms of protein molecules and reconstruct their three-dimensional structures.
  “The protein molecules,” said Prof Zhang, “are extremely complicated because they contain thousands of atoms.”
  One particular scaffold protein being worked on is designated PSD-95. Researchers are also looking closely at the protein, nitric oxide synthase that produces nitric oxide, a gas molecule functioning as a messenger between brain cells under normal conditions.
  In balance, all are important for the normal functioning of the brain but when stroke occurs, loss of oxygen supply in the brain cells causes the production of massive amounts of nitric oxide that is toxic and in turn kills the brain cells.
  “You have a short window of time to re-supply oxygen to the brain otherwise nitric oxide continues to be produced,” said Prof Zhang. “If you don’t treat victims within 10 hours, normally they will have permanent brain damage.”
  The researchers are looking at how to prevent brain cells in stroke victims from killing themselves. They know that PSD-95 and nitric oxide synthase need to come together to produce the nitric oxide gas so one strategy is how to uncouple them in stroke conditions.
  “Currently, there is no cure for stroke. But we believe that what we are doing will provide very important scientific findings for the development of potential stroke treatment, at least to alleviate but potentially to cure or reverse stroke,” said Prof Zhang. “There’s a long way to go and it needs many scientists, clinicians and drug companies to work together on this,” he added.

Principal Investigator
Prof Mingjie Zhang :