Scientists develop novel tools to gain new insights into an important therapeutic target

A team of researchers, led by the Monash Institute of Pharmaceutical Sciences (MIPS) have, for the first time, developed a tool that will enable the wider scientific community to gain a deeper understanding of how the human adenosine A1 receptor (A1AR) works in living cells.

The MIPS study - just published as the cover story in the highly regarded Journal of Medicinal Chemistry - highlights the team’s successful development of a series of versatile tools known as ‘fluorescent ligands’ for the in-depth study of A1AR.

A1AR is an essential therapeutic target, providing a number of opportunities to help treat conditions such as congestive heart failure, tachycardia (heart rate over 100 beats per minute) and neuropathic pain.

However, until now it has remained poorly targeted due to a lack of understanding of how it behaves across tissues, cell types and subcellular compartments.

The highly collaborative study involved Professor Peter Scammells, Associate Professor Michelle Halls and Dr Lauren May from MIPS, along with Professor Stephen Hill and Professor Barrie Kellam from the University of Nottingham. In addition, joint MIPS-Nottingham PhD candidate, Eleonora Comeo, was a central contributor to the study.

Professor Peter Scammells, who is the Medicinal Chemistry Theme Leader at MIPS, said: “In this study we’ve been able to expand the available fluorescent A1AR ligand toolbox, which is an exciting development not only for our team, but also to the wider scientific community seeking to understand the molecular mechanisms underlying A1AR pharmacology in health and disease.”

In terms of what this means for disease, Professor Scammells says that fostering a deeper understanding of A1AR has the potential to significantly improve the way in which certain conditions, such as heart disease, are treated.

Associate Professor Michelle Halls from the Drug Discovery Biology Theme (DDB) at MIPS said: “We’ve essentially gone from not being able to see what’s going on with this important therapeutic target to being able to visualise where these receptors are on a cell. This will transform what we know about A1AR and how it behaves in cells and tissues.”

Dr Lauren May, also from DDB said: “We can use our new tools to visualise the A1AR to work out whether its expression or location changes during disease. Ultimately this knowledge could be used to inform more effective and targeted approaches for the different disease stages.”

This work was funded by the Medical Research Council, the Australian Research Council, the National Health and Medical Research Council of Australia, a Monash Fellowship, a Viertel Senior Medical Research Fellowship, an Australian Heart Foundation Future Leader Fellowship and the Centre of Membrane Proteins and Receptors. It was also supported by the Nottingham-Monash Joint Doctoral Training Centre program.

Contact: Kate Carthew

Phone: +61 438 674 814

Email: kate.carthew@monash.edu