New imaging technique tracks live cells deep within animals’ bodies

Using compounds that create the glow of a fireflys belly,
researchers were able to image cells deep in the brain
of this marmoset for over a year.
The blinking glow, or bioluminescence
of fireflies comes from a chemical reaction
in their lower abdomens.
The reaction varies slightly from species to species
but its all based on an enzyme and a compound
coming together with a little oxygen and ATP
as the reaction goes forward, light is emitted.
Scientists have been using variations on this reaction
for decades to non-invasively observe biological
processes in cells and small laboratory animals
But the light from these systems was not very bright
and needed to be pretty close to the surface to be seen.
Now researchers have engineered a modified
luciferase-luciferin pair
that glows up to 1,400 times brighter.
Researchers used directed evolution
to improve the enzyme’s activity.
They introduced randomly mutated versions
of the enzyme into bacteria, then sprayed
the bacterial colonies with a specialized substrate
the colonies that glowed the brightest
were selected and mutated again.
21 generations later,
the optimized enzyme-substrate pair
glowed much brighter and was less toxic to cells.
The brighter glow was due in part to the fact
that the substrate was engineered to emit light
in a different part of the spectrum --
redder light passes more easily through tissue.
And the evolved enzyme was able to process
the substrate faster-- meaning more glowing
reactions in less time.
These improvements allowed the detection of cells
in living animals much deeper inside the animal
and with more precision.
Using a camera sensitive to near-infrared light,
researchers were able to detect single
transplanted tumor cells in the lung of a living mouse,
the equivalent of detecting a single firefly
in a space the size of a high school gym.
They were also able to monitor the activity
of specific neurons in mice
in reaction to novel environments.
And they followed cells deep in the brain
of a marmoset over the course of a year.
In the future, this new imaging technique
could help scientists learn about where
stem cells end up,
aid in monitoring the success of gene-editing,
and even track tumor growth in cancer patients.
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New imaging technique tracks live cells deep within animals’ bodies

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