Leaving no stone unturned in the race against coronavirus

In the laboratory, Researcher and University of Queensland Laboratory Manager Stacey Cheung. Image courtesy of Ms Cheung.

When an opportunity came knocking to work on a ground-breaking vaccine to combat a global virus pandemic and potentially protect billions of people around the world, Stacey Cheung stepped right up and has not looked back.

Stacey works as part of the team at the University of Queensland’s School of Chemistry and Molecular Biosciences who are one of six Coalition for Epidemic Preparedness Innovations (CEPI) backed organisations researching a vaccine against COVID-19 — building on Queensland’s legacy as a world leader in bioscience and research.

Speaking with Stacey, we found out about the molecular clamp technology that UQ is developing that will help to develop a vaccine to protect our bodies against the coronavirus and the work involved in getting there.

Stacey graduated with a Diploma in Molecular Biotechnology in Nanyang Polytechnic Singapore before undergoing Bachelor of Science (specialising in Immunology & Infectious Diseases) and Honours (Biotechnology) with The University of Queensland. After initially starting out as a Research Assistant with Professor Paul Young, Stacey is now the Laboratory Manager.

Researcher and University of Queensland Laboratory Manager Stacey Cheung at home. Image courtesy of Ms Cheung

Can you take us back to when you first found out you’d be researching for this vaccine?

Over the past few years, I, along with some co-workers in Professor Young’s lab, have been working on this molecular clamp technology with Dr Daniel Watterson and Dr Keith Chappell. After many years of research, our hard work finally paid off! We have success in generating promising vaccine candidates for several important viral infections including MERS, Ebola, RSV, and Influenza, all incorporated with the clamp technology.

This solid data enabled us to be awarded with a three-year grant by the Coalition for Epidemic Preparedness Innovation (CEPI) in 2018, allowing more team members to be recruited and trained to develop on the rapid response technology. The goal was to get the team and pipeline platform ready to respond as fast as possible in the face of an epidemic/ pandemic. The COVID-19 outbreak struck when CEPI was one year into our three-year partnership, the urgency of the situation required all hands-on deck to cover all grounds to move as fast as possible, and that was how I got involved.

How did the team come together?

Professor Paul Young, Dr Daniel Watterson and Dr Keith Chappell are founders and inventors of the molecular clamp technology. Both Dan and Keith were Paul’s undergraduate, Honours, and PhD students so they go a long way back. Professor Trent Munro joined the group last year as CEPI Program Director and brings years of extensive industry experience acquired from the US to the table. Christina Henderson joined as the CEPI project manager. Together with several talented and dedicated post-doctorates, research assistants, and PhD students, we form the antigen design and characterisation team — where generating a vaccine first begins. The worker bees in the laboratory consist of Dr Naphak Modhiran, Dr Danushka Wijesundara, Dr Selorm Avumegah, Dr Christopher McMillan, Julia Lackenby, Summa Bibby, Ariel Isaacs, Connor Scott, and myself. Everyone is passionate, and committed, and plays vital roles towards making the COVID-19 vaccine.

What is your role in the team?

I have a major hands-on technical role. I spend 90 percent of the time doing groundwork in the wet lab performing a wide range of experiments, and the remaining 10 percent operating laboratory management duties such as handling all laboratory consumables and reagents, as well as administrative issues and procurements.

Can you describe what a typical day might look like for you during the research?

For this COVID-19 project, a typical day would be 10–15 hours of work that usually begins between 6–8am. There is high repetition and large quantities of work that requires immense accuracy, focus, and speed. Typical day-to-day experiments include cloning, bacterial colony screening, growing bacterial cultures, performing DNA extractions, cell transfections, protein purification and concentration, running DNA and protein gels, performing biological assays, making media and buffers etc., on top of maintaining and running a laboratory.

It is easy to grow weary very quickly, so it is important to be self-motivated and take breaks where necessary. Personally, I am thankful for a few things that have kept my mental health sane. Everyday, I begin my day with a rush of adrenaline when I jump on my motorbike to go to work. My ride is my therapy, and especially so at the end of a long day. At work, I love that I have a great relationship with my amazing colleagues who are always up for a chat or a laugh. At home, unwinding with pet therapy with my sweet and adorable cats, Dexter and Chester, is just pure bliss. But most of all, nothing beats indulging in delicious home-cooked meals by my personal chef and fiancé, Adrian, he sure knows the ways to my heart.

In the laboratory, Researcher and University of Queensland Laboratory Manager Stacey Cheung. Image courtesy of Ms Cheung.

Can you tell us a bit more about the research technology you are using to develop the vaccine?

To understand how this technology works, we first need to understand how viruses work. Let’s use SARS-Cov-2 for relevance. This virus has a very important feature on its surface, called spike proteins. They function as receptors to bind with and infect other cells. Interestingly, upon binding with other cells, these spike proteins change structure into something unrecognisable, so it has two forms: pre-fusion and post-fusion. The fusion of the viral and cell membranes subsequently releases the viral genome into the cell, resulting in the cell being invaded. In order to make a good vaccine, we need to create these spike proteins in their pre-fusion form, just like how they would naturally appear on the real virus.

For simple illustration, think of the movie ‘Transformers’ where the cars and robots represent the pre-fusion and post-fusion forms of the spike proteins respectively. The clamp technology constricts the spike proteins to be in their “car/ pre-fusion” form for the immune system to recognise them as the “enemy”, because once they transform into “robots/ post-fusion”, they fall off the radar by the immune system and will not be attacked. Our goal is to prevent that so these viruses are eliminated before they can cause any destruction.

Vaccines help develop immunity by imitating an infection. By exposing the immune system to these spike proteins, specific antibodies that are produced will remember how to fight this disease in the future. Utilising the spike proteins alone without any viral genetic material classifies it as a subunit vaccine, and is very safe.

In a nutshell, the molecular clamp technology stabilises the conformational change that the spike protein naturally undergoes and facilitates the expression of recombinant proteins in their native ‘pre-fusion’ form, a state that is recognisable by our immune system for future protection against this virus.

What are the next steps for your research team?

The next steps, now that we have locked in a vaccine candidate, will include lots of pre-clinical assays and trials to verify this construct for safety and efficacy. In order to do so, we need to ensure we have enough materials to work with. Briefly, this means generating high amounts of DNA, extracting and processing them, as they are required for expressing the respective proteins. Then, purifying and concentrating high amounts of proteins before we can validate and characterise them, all of which requires multiple lengthy steps and is therefore extremely laborious.

Do you ever stop and think about the impact your work will have?

Not until now. We have been working as fast as possible in the laboratory where our focus and priority is getting the job done. In saying that, I have always been a strong believer of how vaccines can save lives and how much suffering it can alleviate or prevent, which is the core reason of what has kept me going steadily for the past three months. As brutal as it is, the current tragedy that the world is facing is the result of not having a vaccine against COVID-19, a world without any vaccines would be unthinkable. My contribution to this work could protect millions around the world and prevent them from succumbing to this disease, and that’s phenomenal. However, despite our best efforts, it would still be ideal if the virus can be contained long before a vaccine or cure is available.

What will developing a vaccine mean for Queensland?

Queensland already has worldwide recognition for the success of Gardasil along with other rising researchers, a successful COVID-19 vaccine will build on top of that legacy. This will hopefully bring more attention to the many other talents and amazing research that are happening in Queensland, allowing investors to see the potential in providing additional funding for further fantastic research to continue.

Did you ever consider you could be working as part of a team in one of six organisations in the world (backed by CEPI) to develop a ground-breaking vaccine?

No, I did not anticipate this. I guess I was at the right place at the right time and I am grateful to have the opportunity to work towards creating a life-changing innovation.

What will you do to celebrate if you are successful in developing a vaccine?

To celebrate, I will plan an epic team retreat for some quality rest and relaxation with good food, good wine, and a good time! But before that, a long overdue appointment to the hair and a lash salon, followed by a massage and a spa is definitely needed!

And finally, what would you say to anyone who was looking at a career in Science, Technology, Engineering and Mathematics (STEM)?

I would encourage everyone, irrespective of their age and gender, to pursue their passion or whatever that sparks their interests. Be tenacious to dream big, and also be willing to put in the hard work to make it happen. In science, the lifestyle and working hours are generally pretty flexible. Being on the cutting edge of science and making new discoveries can be very rewarding. Work will not feel like work if you enjoy what you do!

Visit Advance Queensland to learn more about how we are supporting Queensland through the COVID-19 pandemic.

 
Last updated 21 May, 2020
Creative Commons Attribution-NoDerivs 3.0 Australia (CC BY-ND 3.0) ( http://creativecommons.org/licenses/by-nd/3.0/au/ )
 
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