Rapid heartbeat mystery uncovered – thinking outside of the box

Researchers at the Harry Perkins Institute of Medical Research have identified a group of genes that are a likely cause of atrial fibrillation, or the rapid beating of the heart.

More than 33 million patients are affected globally by atrial fibrillation and it is a significant factor in stroke, heart failure and increased rates of death.

The extraordinary part of this research story, is that the cells with this gene are not found in the heart, but in the lung.

The discovery by one of the PhD students at the Perkins was actually incidental to the research he was carrying out.

However, it emphasizes that innovation often comes when least expected and being in an cultural environment that fosters thinking outside of the box is critical for making new discoveries.

The student was investigating a severe rare muscle disease and was hunting for the genes that control muscle movement when he noticed a gene called cardiac actin in some cells in the lung.

He started researching more widely and found that as early as the 1870s there were publications that showed that there are small populations of contractile muscle in the lung.

These heart-like cells surround the pulmonary (lung) veins and its thought their contracting pulse squeezes the vessels that take oxygenated blood to the heart.

They contract to a rhythm, but not to the same beat as the heart.

Research Associate Dr Rhonda Taylor subsequently discovered a 1999 publication that showed this independent beating of cells in the lung could trigger atrial fibrillation in some patients.

It seemed these cells were interfering with the electrical rhythm of the heartbeat.

She then led a team from the Perkins, the Lions Eye Institute and UWA to find out what was causing these cells, in some patients, to do more than just contract. Why were they acquiring an electrical capacity that was interfering with the electrical signals in the heart?

The team thought it might have something to do with the genes of these cells.

They started investigating to see if they could identify which genes are turned on or off in the heart-like cells in the lung.

This was challenging because they are a very small population of cells deeply embedded in the lung, they are hard to reach and hard to isolate to look at them so instead they examined publicly available data and mined it using bioinformatics.

Bioinformatics is a rapidly growing area of science in which researchers “deep-dive” into large and complex data bases to find “needle-in-the-haystack” clues linking genes and outcomes at a speed, courtesy of the new technology, never thought possible previously.

Bioinformatics and systems biology, the science that surrounds it, is transforming 21st century biomedical science.

As a result of their bioinformatics approach, the team was able to identify the group of genes likely to be found in this particular heart cell in the lung.

One of which is a very big lead gene, called Titan, which appears to regulate a number of other genes that could cause the cells to have an electrical function.

This new information, which has now been published, lays the foundation for further work to understand the remarkable connection between these rare lung cells and the beating heart.

Ultimately we hope the discovery of the genes causing atrial fibrillation will lead to new treatments and improved outcomes for patients

This story illustrates the importance of collaboration, lateral thinking and the power of the exciting new technology to transform our way of doing business in biomedical science.