Researchers developed a molecular tool called the Ca2+ BioLuminescence Activity Monitor (CaBLAM) and reported it in Nature Methods. The project grew from the Bioluminescence Hub at Brown University, launched in 2017 with a major National Science Foundation grant. Nathan Shaner at UC San Diego led the development of the molecule that became CaBLAM.
CaBLAM detects calcium-linked activity by producing bioluminescent light inside cells when an enzyme breaks down a small molecule. Because the light is generated internally, experiments do not need bright external illumination. That avoids photobleaching (when a fluorescent molecule stops working), reduces phototoxic effects on cells, and removes the need for hardware such as lasers and optical fibers.
Bioluminescence also stands out against a dark background because brain tissue does not naturally produce it. Although tissue scatters external light and can blur images, engineered neurons that glow by bioluminescence remain easier to see; the team recorded activity for five continuous hours in one example. The Hub is also working on related projects, including using living cells to send light that neighboring cells detect, engineering calcium-based methods to control activity, and creating brighter calcium sensors. At least 34 researchers from partner institutions, including Brown, Central Michigan University, UC San Diego, UCLA and New York University, contributed, with funding from the National Institutes of Health, the National Science Foundation and the Paul G. Allen Family Foundation.
Difficult words
- bioluminescence — light produced by living organismsbioluminescent
- photobleaching — loss of fluorescence after light exposure
- phototoxic — harmful effects of light on living cells
- enzyme — protein that speeds up chemical reactions
- scatter — spread light in many directionsscatters
- sensor — device or molecule that detects signalssensors
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Discussion questions
- What practical advantages might removing external illumination bring to laboratory experiments and equipment costs?
- The Hub plans to use living cells to send light that neighboring cells detect. What possible uses or challenges can you imagine for this approach?
- How could the ability to record activity for several continuous hours change the questions scientists can study about brain activity?
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