Eel Fluorescent Protein Revolutionizes Bilirubin Assay

A fluorescent protein from freshwater eels could serve as the basis for a revolutionary new clinical test for bilirubin, a critical indicator of human liver function, hemolysis, and jaundice.

Bilirubin is a common marker in blood tests where bilirubin is used by doctors to assess liver function and for the assessment of health, including hemolysis, the loss of red blood cells in anemia.

Scientists at the RIKEN Brain Science Institute (Wako, Japan) investigated a fluorescent protein harbored by Unagi (Anguilla japonica) the sea-going Japanese freshwater eel. The team cloned a gene from Unagi for an unusual fluorescent protein they named UnaG, for Unagi Green protein, which allows eels to glow in the dark. UnaG is the first fluorescent protein found in vertebrates; previously they were thought to exist only in simple animals like jellyfish.

The unique nature of UnaG is that it needs a natural chemical to activate its powerful green light emission. The compound was identified by the investigators to be bilirubin, a molecule universally used in clinical laboratories around the world as a human blood marker for liver function. 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. With this property, they developed a superior new assay for bilirubin with high sensitivity, accuracy, and speed that may become the global clinical standard, and can be used in developing countries where child liver health is a major issue.

The scientists performed large-scale measurements comparing human serum samples spiked with bilirubin (UC-BR) and volunteer blood samples and were able to demonstrate the applicability of the fluorescent method while emphasizing the limitations of conventional methodology. Due to the simplicity, they propose that the method will be helpful to clinical laboratories worldwide who run blood panels including bilirubin, and, in particular, pediatricians and pediatric caregivers who treat low birth weight infants in whom high levels of UC-BR may cause jaundice and kernicterus.

Atsushi Miyawaki, MD, PhD, the senior author concluded, “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. 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." The study was published on June 20, 2013, in the journal Cell.

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RIKEN Brain Science Institute