Victor Chang Cardiac Research Institute laboratory

Star Scientist - Dr Alastair Stewart

Nearly five million Australians live with two or more chronic conditions like heart disease. It means we are taking more drugs than ever before, but how these medications interact inside the body is not fully understood. And that’s a concern.

The Institute’s Dr Alastair Stewart is determined to make a whole range of therapeutic drugs not only more effective, but also safer for those that need them.

30 March 2023

Dr Alastair Stewart with his award from NHMRC

Last year Dr Stewart, the Head of the Institute’s Structural Biology Laboratory, got one step closer to his goal after being successful in his application for a highly competitive Emerging Leader Investigator Grant from the National Health and Medical Research Council (NHMRC).

To add to this achievement, Dr Stewart was awarded the Peter Doherty Investigator Grant Award (Emerging Leadership) at the NHMRC Research Excellence Awards dinner in Canberra on 29 March. This award recognises Dr Stewart as the highest-ranked grant applicant in this category.

It’s an impressive achievement to be highlighted as a standout amongst his peers.

Dr Stewart says: “I am incredibly grateful and honoured to receive this award in recognition of this valuable work. In many ways, it is the product of a true team effort from the contributions of my team, collaborators and invaluable support and mentorship from the Institute.

“I hope this award highlights the invaluable contributions of bench-side researchers to medical research and how considerable investment in basic science research infrastructure and capacity can translate to clinical benefits.”

Shedding light on how drug molecules work

The Emerging Leader Investigator Grant will enable Dr Stewart and his team to shed light on how cells transport drug molecules by using cyro-electron microscopy technology based in the Institute’s Innovation Centre.

This will generate detailed information on the precise mechanisms of human drug transporters, providing a template to understand how and why certain drugs interact with each other.

The ultimate aim is to improve safety of a wide range of drugs - including cardiac-related drugs such as hypertension drugs, along with endogenous compounds (such as pain medication), diabetic drugs, chemotherapy agents and recreational drugs.

Dr Stewart says: “Beyond understanding what makes therapeutic drugs effective, this work will also shed light on how some drugs may be toxic unintentionally. By establishing how drugs interact with membrane proteins in our bodies, the information may also feed into drug development by improving safety and effectiveness.”
Dr Alastair Stewart and Dr Carus Lau and  in Cryo Em Microscopy Facility

Carus Lau and Alastair Stewart in Cryo Em Microscopy Facility

Understanding membrane proteins

To improve health outcomes, Dr Stewart’s research focuses on better understanding membrane proteins, which can act as important cellular gatekeepers for drugs.

Dr Stewart says: “Membrane proteins sit on the surface of cells and regulate the movement of molecules in and out of cells. Unsurprisingly, most therapeutic drugs will interact with these membrane proteins, even if it is only to gain entry into the cell. I am keen to understand how membrane proteins work in their natural environment and how drugs interact with them.

“Scientists have long been perplexed by the difficulties studying the structure of proteins, especially the membrane proteins on which my research focuses. Buried within the cell surface, membrane proteins are notoriously difficult to access and study.”

Dr Stewart’s approach to his research relies on the latest novel cutting-edge equipment and research methods.

Dr Stewart says: “To generate a comprehensive picture of membrane protein structures, I use electron microscopy and intensive computational methods to create high-resolution images and data. This helps us understand how large groups of membrane protein’s function and how binding to certain medications can alter their behaviour.”

Finding inspiration at the Institute

Growing up in Cambridge surrounded by academics, you’d think choosing an area of research to dedicate his career to would come easy for Dr Stewart. But as is often the case in life, things weren’t that simple.

Dr Stewart remained undecided on where he wanted to head with his research career until he moved to Australia to undertake a PhD in structural studies at the Institute.

Dr Stewart says: “During my PhD my now-mentor and then-supervisor (former head of the Institute’s Structural Biology Laboratory) Dr Daniela Stock introduced me to the wonderful world of membrane proteins and enzyme mechanisms.

“The way Dr Stock spoke about science captivated my curiosity, and this continues to drive me in my research today.”
Acknowledgement of Country

The Victor Chang Cardiac Research Institute acknowledges Traditional Owners of Country throughout Australia and recognises the continuing connection to lands, waters and communities. We pay our respect to Aboriginal and Torres Strait Islander cultures; and to Elders past and present.

Victor Chang Cardiac Research Institute - The Home of Heart Research for 30 Years