News release

From: QIMR Berghofer

QIMR Berghofer researchers have created the most detailed map yet of the chemical signals that control heart function, opening new avenues for the diagnosis, treatment and prevention of heart disease.

The online resource, called Cardiopedia-Ligand, catalogues how human heart tissue responds to more than 80 biological signals, creating an unprecedented reference tool for cardiac researchers, clinicians and industry.

Published in Cell Stem Cell, the study used miniature human heart tissues grown in the laboratory, known as human cardiac organoids, to test 87 signalling molecules that interact with receptors found on heart cells.

WATCH THE VIDEO EXPLAINER HERE

For each treatment, researchers measured how strongly the tissue contracted and which genes were switched on or off, generating a comprehensive dataset that links biological signalling with heart function and gene activity.

Professor James Hudson, Head of QIMR Berghofer's Cardiac Bioengineering Laboratory, said the atlas fills a major gap in scientists' understanding of how the heart works.

"Before this project, no one had mapped and comprehensively compared each single signalling molecule and its effects on the heart. For the first time, we've brought all that information together into a single resource that researchers can use to better understand heart disease," Professor Hudson said.

Research officer Dr Janice Reid said the project was made possible by the team's human cardiac organoid platform.

“We can produce more than a thousand organoids each week, which allows us to perform studies at a much bigger scale than what has previously been possible," Dr Reid said.

"The cells in the heart are constantly talking to each other using chemical signals known as ligands. These ligands have been explored before, but mostly individually and in very different models. What we've done in this study is compare them all in one go, allowing us to directly compare their similarities and differences," she said.

The atlas has been made publicly available through an online portal, allowing researchers worldwide to explore and analyse the data.

"This project has taken five years to build, generate and analyse. We wanted to make the data free for everyone because we're excited to see how researchers use it and the discoveries it could help accelerate," Professor Hudson said.

"Someone working on a certain ligand might want to look up what it does to function. Another person might want to see what that ligand does to expression of different genes correlated with disease. There's just so many different applications," he said.

The work represents the first phase of a broader initiative supported by the Snow Medical Foundation. The next stage will screen around 2,000 drug compounds to build an even more comprehensive map of heart biology and responses to potential therapies.

Professor Hudson said the long-term goal was to help support more personalised treatment for heart disease.

"Most current heart medications don't directly affect the heart muscle; they affect things like blood pressure and fluid loading," he said.

"The goal is to increase the number of drugs that are effective for heart failure that actually act on the heart tissue. The grand vision of the project is that, for personalised medicine, someone can go to the hospital and their genetics and biomarkers are exactly matched to an effective drug."

Dr Reid said the finished project was exciting for the team. “Similar large datasets exist for diseases like cancer, but not for the heart. We've been able to build the models and pipelines needed to start creating these resources for cardiovascular research, which could lead to more precise answers about heart disease."

Professor Hudson said publication marked the beginning, rather than the end, of the project's impact.

"Most scientific papers bring a sense of completion when they're finished. This one is different. This is the beginning of our resources to accelerate future discoveries."