Fluorescent Protein Identified in Eel Could Revolutionize Testing for Liver Function

Unagi, the Japanese freshwater eel, contains a fluorescent protein that could lead a revolution in clinical testing for bilirubin, a critical indicator of human liver function, hemolysis and jaundice, researchers from the RIKEN Brain Science Institute report in a new study published in the journal Cell.

Best known as delicacy in Japan, the freshwater eel and related species are experiencing a worldwide drop in numbers, likely due to global warming, the scientists explained, and is on the brink of being completely disappearing in Japan.

Yet, nearly nothing is known about the eel’s biology.

For this reason, Atsushi Miyawaki and Akiko Kumagai cloned a gene from the creature for an unusual fluorescent protein they named UnaG, for Unagi Green protein, which allows the eels to glow in the dark.

UnaG is the first fluorescent protein found in vertebrates, challenging the long-held notion that they only exist in simple organisms, such as jellyfish.

What makes the UanG truly unique, however, is that it needs a natural chemical to activate its powerful green light, which, in a surprise twist, the researchers identified to be bilirubin, the slippery molecule universally used in labs around the world.

A breakdown product of blood hemoglobin, bilirubin is toxic if present in excess in the body, such as in the characteristic yellow skin and eye color conditions seen in newborn babies, jaundice and kernicterus. Furthermore, in addition to asses liver function, it can be used to test for the loss of red blood cells in anemia.

By analyzing the structure of UnaG, the team discovered a novel mechanism of fluorescence enabling bilirubin to bind to UnaG and activate its light emission that they have since used to develop a superior new test for bilirubin with sensitivity, accuracy that they believe may become the global clinical standard, especially in developing countries where child liver health remains a major issue.

Given new evidence of a need for the eel beyond the restaurant industry, the researchers believe the discovery may act to initiate legislation to conserve the endangered eel species.

“We believe that UnaG provides an unexpected foothold into several important but currently obscure areas of human health, including bilirubin metabolism and muscle physiology during endurance exercise,” Miyawaki said, referencing the unagi’s long-distance migration lifecycle, growing in inland rivers and swimming far into the sea to spawn.

Moreover, the researcher explained, their overall reaction is simply one of surprise.

“Before the discovery of UnaG, I couldn’t imagine that basic science could have such a direct impact on human health,” he said. “From a simple eel, we found a new path to the clinic.”