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Revolutionary nanotechnology illuminates brain cells at work

Until now it has been impossible to accurately measure the levels of important chemicals in living brain cells in real time and at the level of a single cell. Scientists at the Carnegie Institution's Department of Plant Biology and Stanford University are the first to overcome this obstacle by successfully applying genetic nanotechnology using molecular sensors to view changes in brain chemical levels. The sensors alter their 3-dimensional form upon binding with the chemical, which is then visible via a process known as fluorescence resonance energy transfer, or FRET. In a new study, the nanosensors were introduced into nerve cells to measure the release of the neurotransmitter glutamate--the major brain chemical that increases nerve-cell activity in mammalian brains. It is involved in everything from learning and memory to mood and perception. Too much glutamate is believed to contribute to conditions such as Alzheimer's and Parkinson's disease. The research is published in the May 30-June 3 on-line early edition of the Proceedings of the National Academy of Sciences.

"The fluorescent imaging technique allows us to see living cells do their jobs live and in color," explained Sakiko Okumoto, lead author of the study at Carnegie. "Understanding when and how glutamate is produced, secreted, reabsorbed, and metabolized in individual brain cells, in real time, will help researchers better understand disease processes and construct new drugs."

"FRET is like two musical tuning forks, which have the same tone," Okumoto continued. "If you excite one, it gives a characteristic tone. If you bring the second fork close to the first one, it will also start to give you a tone even though they do not touch. This is resonance energy transfer."

FRET is used to track the form of proteins that specifically bind metabolites such as sugars and amino acids. A protein of interest is genetically fused with two differently colored tags made from variants of the jelly
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Source:Carnegie Institution


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