Dr Alastair Stewart Victor Chang Cardiac Institute

Dr Alastair Stewart The Butterfly Collector

Dr Alastair Stewart has been on the path to discovery ever since he moved from Cambridge to Sydney

What began as a journey of self discovery has led to the biggest breakthrough in his career as a structural biologist.

26 May 2020

Along the way he found the love of his life, realised the joys of fatherhood and recently made an unusual finding in the field of entomology. But above all Dr Alastair Stewart has discovered that life is full of surprises.

Congratulations on your recent paper published in Nature Communications, what have you discovered?

We’ve been able to image a biological energy generator in exquisite detail. This generator is responsible for making the majority of energy in cells and is called F1Fo ATP synthase. We took thousands of images, each containing hundreds of ATP synthase molecules frozen in a thin film of ice. Analysing hundreds of thousands of individual molecules showed us how this generator flexes and moves in solution, providing a potential mechanism of how motors are able to couple rotating and stationary elements. It’s just like the engine in your car which uses springs and oil to lubricate moving parts, these motors need physical properties that allow them to function efficiently. The paper is called 'Cryo-EM structures provide insight into how E.coli ATP synthase accommodates symmetry mismatch'.

This is the biggest breakthrough of your career to date, why is it so significant?

Understanding how life converts energy is of great fundamental importance. Without energy biological processes can’t function and life could not exist. One day we hope to be able to use information on these molecules to design novel antibiotics that interfere with bacterial molecules and not the human ones. Also, as we were able to image the bacterial enzyme from E. coli (a common laboratory organism), we hope that the insights gained in this study will help many other researchers design experiments to understand the inner workings of this fabulous machine.

An electron micrograph containing ATO Synthase

These are two images from the Nature Communications paper. On the left is an image of an electron micrograph containing “ATP synthase” molecules frozen in ice (identifiable by the small dark dumbbell objects). The width of this image is roughly one-hundredth the width of a human hair and the pixels had a calibrated size of one ten-billionth of a metre. The image on the right shows an averaged many of these molecules. Each coloured object is a different molecule that comes together to form a “complex”.

What made this breakthrough possible?

Well first of all, it wouldn’t be possible without my great team. Dr Meghna Sobti in particular has driven this project for the last five years. The Institute and the NHMRC have also given us generous support to understand this basic biological process. Moreover, our new Innovation Centre at the Victor Chang Cardiac Research Institute recently installed a cryo-Electron Microscope, and quick easy access to this instrument has allowed us to improve our sample preparation techniques. Finally, the ultimate high-resolution data collection was taken over at the PNCC in the United States and Dr Craig Yoshioka there gave us plenty of knowledge and advice to get this project working.

What inspired you to pursue a career in structural biology?

I’m not sure I ever pursued a career in structural biology. Both my parents were biologists, so if anything I think I was encouraged to stay as far away from structural biology as possible. Instead, as with most things in life, I stumbled across a love for biophysics when I began volunteering here at the Institute with my future PhD supervisor Dr Daniela Stock. Daniela showed me how to have fun in the lab and enjoy what I was doing.

Dr Stewart with his mentor Dr Daniela Stock

Why did you decide to relocate from the UK to Australia? What did you do when you first arrived?

I really just came to Australia for a holiday, I was a bit of a lost soul after my undergraduate degree at Cambridge and I needed a new start. Having Australian parents meant that I always had a connection with this country and I wanted to come here to spend time with my extended family and explore the country. When I first arrived, I was living in my aunt’s garage (Wayne’s World style) and volunteered with her to do some wildlife conservation. This group of volunteers spends a few days a week regenerating the bushland up on the North Shore of Sydney, to improve the habitat for the flying foxes that call it home. That was a tremendous way to begin my time in Australia, working under these huge bats and learning about them and the native flora on the ground. I still have great memories of sitting next to wild orchids, while drinking fresh lemon myrtle tea under those huge flying dog-like creatures.

It must have been hard to start over? You’ve described yourself as a “lost soul” at this point in your life. Why is that? How did you find your way?

I don’t think I ever saw it as hard to start over. I was lucky enough to have family here, so I already had a good support network. And I was always so busy exploring this country, which although familiar to me, was all still new and interesting. I think I described myself as a lost soul before, as I didn’t really enjoy my life in England. Among other things, my mother passed away when I was a teenager and there were many things that reminded me of that time over there. Coming to Australia allowed me to leave some of that behind but remember the good parts like holidays over here. Australia welcomed me with open arms, and when I began to run out of savings while volunteering with the bat group, Daniela offered me a role in her laboratory and the institute opened its arms as well.

How long have you been at the Victor Chang Cardiac Research Institute?

I’ve been at the Institute for over 12 years now on and off. I started as a volunteer, then a Research Assistant, PhD student, Post Doc, Group Leader and now Faculty, so there aren’t many scientific roles I haven’t done here. I even met my wife Laura here, who started as an honours student in the adjacent lab shortly after I started. We now have two children, so the Institute is certainly a large part of my life beyond the research.

Dr Stewart And His Family

Recently your love of animals has led you to another more unusual discovery? Tell us about this.

It did, back when I was a Post Doc at the Institute, I stumbled across a crazy looking moth on our driveway. The thing was as big as my hand and shaped like a delta wing aircraft. I discussed it with one of my bird watching colleagues and after a long time searching for it in the online catalogues, we couldn’t identify it. In desperation, I sent a photo of it to the head of entomology at the Australian Museum and he quickly replied saying it was a female hawkmoth termed Coequosa australasiae.

He also noted that they’d been trying to catch a female for a few years, and asked if I could carefully pick it up and place it in a holey shoe box lined with tissue paper. Luckily the critter had hardly moved when I got home, so I carefully collected it and gave it some twigs for company. Overnight she rustled around in the box and laid hundreds of beautiful bright green eggs.

The next day I took the box to the museum and they sent the eggs to three different locations around the country to document the life story (development stages) of the specimen.

Left: Book cover of Hawkmoths of Australia | Right: photo of the Coequosa australasiae hawkmoth Dr Stewart discovered

This year CSIRO Publishing released a book, Hawkmoths of Australia, describing most of the hawkmoths found across Australia with a Coequosa australasiae on the cover. It was fantastic to learn about something new and feel like I’d helped out someone else’s research.

In Cambridge, people used to tease the biologists, calling them “nothing but butterfly collectors”. Now that I have collected a moth for research and seen the great work entomologists do, I’m going to wear this term as a badge of honour for the rest of my scientific career.

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.

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