Deep look
Bioluminescence is a property of some living organisms to glow. This is the result of the catalytic action of the enzyme luciferase of firefly beetles on D-luciferin. At the same time, a yellow-green glow is produced.
They have tried to use bioluminescence in clinical practice more than once. A group of Japanese scientists decided to use this ability to visualize tissues and cells of the body. They isolated the glowing molecules and amplified them, making the glow hundreds of times brighter. The biomodified glow source was tested in experiments on mice and monkeys.
There have been many attempts to make the process of interaction of luciferase and D-luciferin more effective. For example, by replacing luciferin with a synthetic analog, some scientists have tried to accelerate the catalytic reaction. Atsushi Miyawaki and his colleagues went even further and, combining both components, created a bioengineered bioluminescence system for use in vivo.
Bioluminescence in mice obtained by intravenous administration of HeLa cells producing the Fluc protein (left) and the Akaluc protein system (right). The distribution of the substrate in the abdominal cavity was evaluated. Source: RIKEN.
It was known from previous studies that synthetic luciferin AkaLumine-Hcl is able to penetrate the blood-brain barrier and give a red glow. The problem was that AkaLumine-Hcl is not compatible with natural luciferase.
The researchers sequentially modified the enzyme luciferase with mutations, eventually achieving a fully compatible with AkaLumine-Hcl variant, which was named Akaluc.
When entering the brain of mice, the combination of Akaluc and AkaLumine-Hcl (AkaBLI system) during interaction led to bioluminescence, which was 1000 times stronger than that obtained as a result of the reaction of natural luciferase and luciferin.
Bioluminescence in the brain of mice, obtained one month after the introduction of cells producing the protein Fluc (left), and systems with the protein Akaluc (right). Source: RIKEN.
Bioluminescence can be achieved quite easily, for example, by oral administration of the AkaBLI system with drinking water. But the injection gave a more intense glow.
In an experiment with monkeys, researchers observed brain activity using the AkaBLI system during training and skill formation for more than a year.
AkaBLI-generated bioluminescence allows you to observe the activity of the brain and the dynamics of changes over a certain time. Given the inaccessibility of brain structures for diagnostic studies, noninvasive and safe imaging has great potential for use in clinical practice.
Article by S. Iwano et al. Single-cell bioluminescence imaging of deep tissue in freely moving animals is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: In living color: seeing cells from outside the body with synthetic bioluminescence.