Eel fluorescent protein transforms clinical assay

A Japanese freshwater eel called unagi possesses a fluorescent protein that could revolutionise a key clinical assay for bilirubin, a critical indicator of liver function, haemolysis and jaundice.

A team from the RIKEN Brain Science Institute cloned a gene from unagi for an unusual florescent protein they named UnaG (Unagi Green Protein) that allows eels to glow in the dark. This is a remarkable discovery as it was previously believed that fluorescent proteins only existed in simple animals like jellyfish.

“We believe that UnaG provides an unexpected foothold into several important but currently obscure areas of human health,” said Dr Atsushi Miyawaki who co-led the research.

What makes UnaG particularly special is that it needs a natural chemical to activate the powerful green light emission. The team identified this compound to be bilirubin, a molecule universally used in clinical laboratories as a human blood marker for liver function.

Bilirubin is the breakdown product of haemoglobin which is toxic if present in excess in the body. It’s responsible for the characteristic yellow skin and eye colour conditions seen in new born babies, jaundice and kernicterus.

The team analysed the structure of UnaG and discovered a novel mechanism of fluorescence enabling bilirubin to bind to UnaG and activate its light emission.

This enabled the researchers to develop a superior assay for bilirubin with high sensitivity, accuracy and speed that may soon become the global clinical standard. It could also be used in developing countries where child liver health is a major concern.

Unagi are best known as a culinary delicacy in Japan but the species has seen a worldwide decline in population, possible due to the effects of climate change.

The authors of the study indentified UnaG and bilirubin in the muscle cells of Japanese, American and European eels where they may aid in endurance swimming during  migration. The surprising discovery of UnaG may initiate legislation to conserve endangered eel species.

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

The research is published in Cell.