Dr Alastair Stewart, Head of the Institute’s Structural Biology Laboratory at the Victor Chang Cardiac Research Institute (VCCRI) focuses his research on understanding the mechanisms of how cells transport drug molecules using cyro-electron microscopy technology. Based within VCCRI’s Innovation Centre, Dr Stewart’s research involves generating detailed information on the function of membrane protein structures, providing a template to better understand drug interactions within the body. Read on to find out more about Dr Stewart’s research, in his own words.
Growing up in Cambridge and surrounded by academics, I was exposed to the world of research but had not identified a topic that I could devote my career to. This changed during my PhD when my supervisor introduced me to the wonderful world of membrane proteins and enzyme mechanisms. The way my now-mentor, and then-supervisor, Daniela Stock spoke about science captivated my curiosity and this continues to drive me in my research today.
Scientists have devoted much effort towards studying the structure of proteins, as this information is key to understanding their chemical properties.
Buried within the cell surface ‘membrane proteins’, on which my research focuses, are notoriously difficult to access and study with the tools needed to study them only recently developed.
As workhorses of a living cell, membrane proteins are instrumental in almost all biological processes. Membrane proteins sit on the surface of cells and regulate the movement of molecules in and out of cells in an effort to maintain homeostasis. Unsurprisingly, most therapeutic drugs will interact with these membrane proteins, even if it is only to enter the cell.
I want to understand how membrane proteins work in their natural environment and how drugs interact with them.
My research approach combines pressing problems of our times with the latest novel, cutting-edge equipment and research methods. This generates valuable data on which the research community can rely and build on. To generate a comprehensive picture of membrane protein structures, I employ electron microscopy coupled with intensive computational methods to create high-resolution images and data that describes both how large assemblies of membrane proteins function, and how binding to certain medications can alter individual and collective behaviour.
Receiving an Investigator Grant at this stage of my career is a significant achievement and will allow me to expand my laboratory’s focus on important membrane proteins in bacteria and humans which are often the target of antibiotics.
Beyond understanding what makes therapeutic drugs effective, this work will also shed light on how some drugs may be toxic unintentionally.
By establishing a library of data on membrane proteins, the information will also feed into drug development to identify new drugs and drug targets.
I am incredibly grateful and honoured to be receiving 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 Victor Chang Cardiac Research 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.
