Scientists invent new dye to shine light on disease

Scientists at La Trobe University have developed a novel research tool which better shows how the body processes and stores fat, opening the possibility for new research directions of many diseases including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), heart disease and several types of cancer.

Published in Advanced Sensor Research, the cross-disciplinary team of chemists and cell biologists from the School of Agriculture, Biochemistry and Environment (SABE) and the La Trobe Institute for Molecular Science (LIMS) created a new sensitive fluorescent dye called AM-QTPA which lights up lipid droplets (LDs) – cellular structures in the body which play an essential role in fat processing and storage.

They then conducted proof-of-concept experiments, testing the dye on both healthy tissue samples and samples from donors who had been diagnosed with ME/CFS.

The tests revealed that those with the disease had larger but fewer LDs in their connective tissue, which suggests a link between ME/CFS and how the body processes and stores fat – a previously unknown detail which potentially opens new avenues of research.

Lead author Dr Siyang Ding said the study demonstrates that AM-QTPA is an excellent LD imaging agent and provides an alternative for LD researchers.

“The high sensitivity and great photophysical performance of AM-QTPA will enable high-powered research into the new role of LDs in health and disease” Dr Ding said.

LD abnormalities are implicated in many diseases as well as ME/CFS, including heart disease, non-alcoholic fatty liver disease, neurodegenerative diseases, obesity, some viral infections and many cancers.

However, detailed investigation into how LDs behave can be difficult as current methods such as transmission electron microscopy (TEM) are limited to small sample sizes and cannot be used on living cells. Other existing fluorophores for LDs either do not glow bright enough or are too sensitive to light to create a clear image in a disease scenario.

In developing AM-QTPA, the research team sought to solve these issues by creating a dye that not only specifically highlights LDs, but also glows brightly, can withstand exposure to light and, importantly, can be used in live cell samples derived from patients.

Dr Sarah Annesley, who contributed to the proof-of-concept experiments, said these improvements made it possible to observe LD behaviour over time – a critical improvement which allowed for more detailed observation than was previously possible.

“As we could use the AM-QTPA with live cells, LD dynamics could be measured. This revealed frequent contacts of lipid droplets with the mitochondria – the cell’s powerhouse – which is likely occurring to support the transport of fatty acids from the LDs to the mitochondria for energy generation,” Dr Annesley said.

With the dye successfully used in the context of ME/CFS disease, the study can now be expanded to encompass other diseases where metabolic defects are implicated.

Associate Professor Yuning Hong, corresponding author for the research paper, anticipates AM-QTPA will open many opportunities to deepen disease knowledge.

“This project is an exciting cross-disciplinary collaboration that marries new chemistry techniques with expert cell biology methods to ask new questions in the study of human disease,” she said.

This research was conducted in collaboration with scientists at The Chinese University of Hong Kong.

Read the paper here.