QIMR Berghofer researchers have created a detailed new map of the chemical signals that influence heart function, in a development that could help accelerate the discovery of new treatments for heart disease.
The online resource, Cardiopedia-Ligand, catalogues how human heart tissue responds to more than 80 biological signals. Built using miniature human heart tissues grown in the laboratory, the atlas brings together functional and genetic data in a format designed for researchers, clinicians and industry.
Published in Cell Stem Cell, the study examined 87 signalling molecules that interact with receptors on heart cells. For each treatment, researchers measured the strength of tissue contraction and tracked which genes were switched on or off, producing a dataset linking biological signals with heart function and gene activity.
Professor James Hudson, Head of QIMR Berghofer's Cardiac Bioengineering Laboratory, said the resource addressed a significant gap in scientists’ understanding of the heart.
"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.
The work was enabled by the group’s human cardiac organoid platform, which can produce more than 1,000 organoids each week and allows experiments to be performed at a scale previously out of reach.
Research officer Dr Janice Reid said the project enabled direct comparisons between ligands that had previously been studied largely in isolation and across different experimental models.
"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 is publicly available through an online portal, giving researchers around the world the ability to interrogate how particular signals affect cardiac function and disease-associated gene expression.
"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.
The project is the first phase of a broader Snow Medical Foundation-supported initiative. The next stage will screen about 2,000 drug compounds, creating a larger map of heart biology and the way cardiac tissue responds to potential therapies.
Professor Hudson said the longer-term ambition was to support more personalised approaches to heart disease, including treatments that act directly on heart muscle.
"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 comparable large-scale datasets had transformed research in other disease areas, particularly cancer, but had not previously been available for cardiovascular research.
"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."
For Professor Hudson, publication marks the beginning of the atlas’s potential impact rather than its conclusion.
"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."
