Science's Big Ideas: Australian University Science issue 7

Issue 7, Mar 2022

SCIENCE’S BIG IDEAS The critical impact of fundamental research in Australia

Biology’s next revolution is coming, p3 Future-proofing us from cancer and COVID, p5 Why basic science matters, p6

Developing new industries Training the future workforce | Leading in innovation

The case for curiosity

Investing in fundamental research is vital for Australia’s edge in innovation.

Much research is driven by curiosity. This is often thought of inappropriately as ‘blue-sky’ research — the stereotypical scientist in their lab, pursuing their personal interest, with little or no thought to the utility of the outcome.

In reality, curiosity-driven research is generally undertaken because the researcher wants to understand something puzzling about us and our world. The answers to these puzzles can provide huge leaps in knowledge and often lead to translatable research outcomes that have a profound impact on society.

My own research segued from renal medicine to an interest in immunology and pathology, and subsequently into the way the body recognises and responds to genital warts — which are caused by one of the more-than-200 types of human papilloma viruses (HPV).

The last part of the 20th Century saw genomics come of age. Basic, curiosity-driven research into papilloma viruses, and the way these viruses incorporate their genetic information into the DNA of infected cells, led to the discovery that viruses can be responsible for cervical and other cancers. In 1990, Chinese virologist Dr Jian Zhou and I cloned the genes for the papillomavirus surface proteins and expressed them in cells, using knowledge drawn from decades of work on the smallpox virus.

Some viruses, including HPV, can be difficult to grow in the lab, so instead we used our understanding of the HPV genome to develop a method to encourage HPV proteins to selfassemble into virus-like particles — provoking a host immune response and enabling a vaccine that prevents HPV-associated cervical — and other — cancers.

That vaccine, Gardasil, was approved by the Therapeutic Goods Association in 2006. A year later, Australia became the first country to roll out a national HPV vaccination program.

Hundreds of millions of people worldwide have now received this vaccine. Research that began with basic science, and benefitted from continuous engagement with basic science, eventually showed both a commercial outcome and a practical benefit: saving lives.

But basic science is far more than the translatable research outcomes it might enable. It is also the catalyst for significant advances in our social and economic wellbeing. Fundamental

“SCIENCE IS NOT LINEAR: IT PROGRESSES MORE LIKE A ROLLER COASTER, IN LEAPS, BOUNDS AND LOOPS, WHILE KEEPING THE TRAIN OF HUMAN PROGRESS ON TRACK.” mathematical analysis of signal processing research led to the internet, while basic physics underpins the giant radio telescope arrays now operating in Western Australia. CRISPR research has had a dramatic impact on plant and human biology, and the development of quantum technology has likewise impacted energy production and computer technology. In short, curiosity-driven research happening at university science departments around Australia has delivered significant practical changes in our lives over the last several decades.

Science is not linear: it progresses more like a roller-coaster, in leaps, bounds and loops while keeping the train of human progress on track.

The technologies, engineering and health benefits we will rely on in the next decades will only happen through continued support of the basic ‘blue-sky’ research at Australian universities happening today.

Professor Ian Frazer AC

The University of Queensland Diamantina Institute and Institute for Molecular Bioscience

AUSTRALIAN UNIVERSITY SCIENCE

Exploring the achievements of university science in building Australia’s sovereign capability Australia’s strong science research and training is integral to driving new economies. Universities have a critical role as partners in establishing innovation and technological change in industry. As science delivers new insights and tools, new industries are emerging, and people with science skills will be

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essential to these new industries. Australian University Science magazine highlights these stories, showcasing exceptional science teams and Australian science graduates working in industry. To provide feedback or suggestions, subscribe or order additional copies, visit acds.edu.au/AustUniScience.

Cover Image: SPL Published 24 Feb 2022 by Refraction Media on behalf of the Australian Council of Deans of Science. Designed by Jon Wolfgang Miller. Printed in Australia by IVE. ISSN: 2652-2403. © 2022 Australian Council of Deans of Science, all rights reserved. No part of this publication may be reproduced in any manner or form without written permission. If you would like to reproduce anything from this issue, email info@refractionmedia.com.au.

topic

Prof Claudia Vickers is championing the evolution of a whole new biology.

BIOLOGY’S MONUMENTAL EVOLUTION From fundamental cellular studies in the 1950s, synthetic biology will become a multi-billion-dollar opportunity in coming decades.

For Dr Yu Heng Lau, bacteria are like tantalising boxes of microscopic Lego.

Most bacterial cells host proteins that assemble themselves into cage-like compartments housing chemical reactions and metabolic processes. In his lab at the University of Sydney, Lau and his team are exploring how to re-engineer these protein cages into tiny factories that could manufacture new and improved medicines, materials and catalysts.

One of Lau’s main projects is designing protein cages that can convert carbon dioxide into useful products such as biofuels. This involves building simpler, customised versions of the photosynthetic architecture found in cyanobacteria. “We basically want to mimic and improve on this natural process,” says Lau. Getting this carbon-fixing hack to function in the real world requires a deep understanding of how biology works at its most basic level, says Lau. This means answering key questions, such as how enzymatic reactions behave inside protein cages and, ultimately, whether they can be planted inside a cell. “What we’re most interested in as a lab is understanding the fundamentals of how biology puts things together,” says Lau.

CREATING A NATURE-ENHANCING TOOLKIT

Lau’s plug-and-play approach to solving health, energy and agricultural challenges is a textbook example of synthetic biology in action. Synthetic biology has its foundations in the 1953 discovery of DNA’s structure, and builds on the vision of scientists like Waclaw Szybalski in the 1970s to move from a “descriptive phase” (looking at the biology that exists) to a “synthetic phase” (devising and building whole new genomes).

As recombinant DNA technology became more sophisticated, scientists moved on from simply transferring threads of genetic material from one organism into another and began modifying and combining sequences to program fresh biological functions.

By the early 2000s, researchers began approaching biology like an integrated circuit, simplifying it so it could be easily tweaked or bolted together from scratch. Applying this classical engineering philosophy to living systems laid the foundation for creating standardised genetic building blocks, taking synthetic biology from a seemingly far-fetched idea to a platform technology.

Today, thanks to massive advances in basic research into genetic engineering, synthesis and sequencing technologies in the past half century, synthetic biology is achieving these visions of functional systems built out of DNA, proteins and other organic molecules.

Researchers working in this rapidly growing discipline are molecular biologists, geneticists and chemists, who are developing practical solutions ranging from mRNA vaccines for COVID-19 to plant-based meat that “bleeds”.

“We operate in these classical engineering faculties of design, build, test and learn,” says Professor Claudia Vickers, a molecular biologist who did her PhD at the University of Queensland and is now director of CSIRO’s Synthetic Biology Future Science Platform.

FUELLING THE NEXT BIOLOGICAL REVOLUTION

The economic potential is huge. By 2040, this burgeoning field of science could generate $27 billion a year and create 44,000 jobs. Over the past two decades, Australian university science has fuelled the field’s meteoric rise from a fledgling discipline to a powerhouse already delivering real-world outcomes.

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topic Macquarie University’s Dr Tom Williams is working on developing the first synthetic yeast genome.

“BY THE EARLY 2000S, RESEARCHERS BEGAN APPROACHING BIOLOGY LIKE AN INTEGRATED CIRCUIT, SIMPLIFYING IT SO IT COULD BE EASILY TWEAKED OR BOLTED TOGETHER FROM SCRATCH.”

The 2016 iGEM team from Macquarie Uni worked on creating hydrogen gas from solar using syn bio techniques.

From the beginning, university students were breathing life into the new science.

In 2007, students from the University of Melbourne were the first Australian team to participate in the International Genetically Engineered Machine (iGEM) competition, which challenges students to use synthetic biology to solve problems, from developing new fuels to creating sustainable materials for fashion, and investigating drought resilience in crops.

Now, 20 universities include synthetic biology in their research programs. Ten of these are affiliated with the ARC Centre of Excellence for Synthetic Biology, headquartered at Macquarie University in Sydney. “It’s been really powerful and quite exponential in terms of building and growing the field in Australia,” says Vickers.

SYNTHETIC BIOLOGY IMPACTS • Ability to rapidly test vaccines and develop ‘smart’ synthetic RNA vaccines • Developing new drought- and pesttolerant crop varieties • Suppressing or stimulating immune responses in cancer therapies • Low-carbon-emitting advanced manufacturing of vitamins, medicines and industrial chemicals • Sustainable production of biofuels and oils • Developing artificial photosynthesis for fuel and chemicals

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SYNTHETIC GENOMES

While solving real-world problems is the driving force of synthetic biology, fundamental science is the engine powering it. To design a tailor-made biological circuit, researchers need to develop a set of rules that enable them to predict and control the components they’re working with. But unlike bolting together an electrical circuit, biology is often a mess of complexity and unknowns.

“If you don’t understand a system, it’s very hard to build it predictively,” says Vickers. “To do that, you need to understand the fundamentals of biology.”

For almost a decade, Dr Tom Williams has been busy trying to grasp the fundamentals of yeast, synthetic biology’s superstar organism. Based at Macquarie University, Williams is a research fellow working on Yeast 2.0 — an international consortium of universities building the first synthetic eukaryotic genome.

Rather than synthesising the yeast genome in its entirety, Williams and his colleagues are figuring out how to create a stripped-down, minimal genome that includes only functional genetic components. This streamlined yeast strain will have a built-in system that allows nonessential genes to be deleted, inverted, duplicated or shuffled at the flick of a switch, paving the way for genetic combinations nature has never seen before.

“Although we’re making one synthetic genome to begin with, we have the capacity to make infinite versions of it in the future,” says Williams, who completed his PhD at the University of Queensland in 2014, making him one of Australia’s first synthetic biology postgraduates.

CREATING NEW FUELS FROM SCRATCH

Yeast is already an industrial workhorse, with US biotech company Ginkgo Bioworks tinkering with its genetic make-up to produce chemicals, pharmaceuticals, foods and other materials. Vickers is also stretching yeast beyond its traditional ‘beer, bread and wine’ capabilities, with her team exploring how it can be used to sustainably manufacture isoprenoids, the largest class of natural organic plant compounds, which are used to create valuable products like biofuels and industrial chemicals.

Once complete, the versatile Yeast 2.0 genome could be customised to create valuable products more efficiently than standard strains. Building the synthetic strain chromosome by chromosome could also help answer big questions in biology, such as how much genomes can be trimmed down.

While synthetic biology is set to become a handy tool for solving massive global challenges, fundamental research will remain at the heart of the discipline, particularly when it comes to training tomorrow’s bright minds, says Williams.

“Synthetic biology really builds on decades of fundamental research in genetics, biochemistry and microbiology,” he says. “On top of that, fundamental research trains the people that are required for the field to make an impact in industry.”

— Gemma Conroy

profiles

CRISPR: FROM CANCER TO COVID Building on fundamental gene technologies, Australian scientists have adapted a treatment for children’s cancer into a tool to target and suppress the virus that causes COVID-19.

CRISPR is a powerful gene-editing tool used by bacteria in their arms race against viral infection. The term was coined by Spanish microbiologist Francisco Mojica in the 1990s; by 2010, microbiologists had shown that the CRISPR-associated protein CRISPR-Cas9 acts as molecular “scissors” to precisely cut and edit DNA. In 2015, Russian-US PhD student Sergey Shmakov identified CRISPRCas13, a protein that edits RNA rather than DNA, reducing the risk of unintended effects on non-targeted genes.

When Cas13 was discovered, Dr Mohamed Fareh was a postdoctoral researcher at the ​​Delft University of Technology in the Netherlands.

“I was really interested in understanding the molecular mechanisms bacteria deploy to fight invading viruses,” he says.

Fareh joined Melbourne’s Peter MacCallum Cancer Centre (Peter Mac) in 2018. In 2019, he and Professor Joe Trapani collaborated with the Children’s Cancer Institute in Sydney to show that Cas13 could successfully eliminate the abnormal RNA that drives a range of childhood cancers.

FROM CANCER TO COVID-19

When the COVID-19 pandemic hit in early 2020, Fareh had a “bold and wild idea” to reprogram the CRISPR-Cas13

MOHAMED FAREH

Research assistant, University of Nice Sophia Antipolis, France

Dr Mohamed Fareh was able to flip his research into children’s cancer treatments to new methods for antiviral drugs.

tool to silence the SARS-Cov-2 virus behind the disease.

“SARS-Cov-2 is an RNA virus, so it was a perfect target,” he says.

When the SARS-Cov-2 viral sequence was released by scientists in Wuhan, Fareh and his team at Peter Mac were able to design guide RNA that reprogrammed the CRISPR tool to target small, non-replicating segments of the SARS-Cov-2 genome.

Fareh then approached Professor Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, co-located with Peter Mac at the University of Melbourne. Together with virology postdoctoral researcher Dr Wei Zhao, Lewin and Fareh were able to show that CRISPR could achieve more than 90 per cent suppression of the live virus in infected mammalian cells.

GAME-CHANGER FOR PANDEMICS

The CRISPR-Cas13 tool targets the SARS-Cov-2 genome and cuts it, stopping the virus from replicating. The researchers have demonstrated that the CRISPR tool remains robust when

Postdoctoral researcher, Delft University of Technology, Netherlands

combatting viral mutations.

“Even if the virus mutates, the tool remains effective. We can target different strains with a single drug,” Fareh says.

He says the work is a game-changer for future pandemics. Traditional antiviral drugs target proteins and are extremely challenging to develop in a short period of time. In contrast, the CRISPR-Cas13 tool can be reprogrammed rapidly to fight other viruses such as influenza, Ebola, HIV and many more — as long as the virus’ genome is known.

“We can quickly reprogram it to target any new virus that may emerge in the future,” Fareh says.

As scientific understanding of CRISPR and its associated proteins evolves, more life-saving treatments will be developed.

Fareh says there is a continuum between basic and translational science at Peter Mac and the Doherty Institute.

“When you master basic research, it gives you unique opportunities to translate it to something important, like targeting viral or tumour cells,” he says.

— Nadine Cranenburgh

Senior research fellow, Peter MacCallum Cancer Centre, Melbourne

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spotlight

THE CASE FOR BLUE-SKY SCIENCE Translational research is seen as the endpoint, but innovation, impact and income come as much — if not more — from fundamental science at Australian universities.

Good science, at its core, is a marriage of imagination and application; the synthesis of a wild idea and a mind rigorous enough to prove it. The Australian scientific landscape is replete with original and world-changing innovations: the Cochlear implant, cutting-edge immunotherapy, spray-on skin, the ultrasound, the pacemaker. We have scientists making world-first breakthroughs in quantum computing, agricultural innovations to combat climate change, inventions that will shape the very nature of the ‘new space race’, and game-changing discoveries in nanofabrication and genetics.

Despite punching above our weight in terms of creative discovery, our research community has for many decades shouldered the critique that we are all brains and no bank. As such, commercialisation has become a critical focus of the contemporary Australian research community, as well as the

“IT’S NEARLY IMPOSSIBLE TO PREDICT THE IMPACT OF RESEARCH WHEN YOU DO IT.”

Metal Organic Frameworks are a new class of compounds that stem from basic chemistry research.

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policy of successive Federal and State governments to varying degrees of success. Most recently, the Morrison government made the decision to pressure the Australian Research Council to restrict the majority — a whopping 70% — of its grant funding to six key manufacturing priorities.

These include space, defence, recycling and clean energy, medical products, food and beverage, and resource and mining tech.

Translating innovation into viable commercial endeavours is important, but there is also a strong case to be made for the long-term, often unpredictable value of fundamental, ‘blue-sky’ research.

While investment in fundamental research is consistently a much smaller percentage of research budgets, it underpins the most revolutionary — and often most lucrative — outcomes. While OECD countries devote just 22% of their research budgets to basic research, one study found that approximately 80% of medicines, for example, could trace

their origins to “one or several basic discoveries”.

“Whether you’re in the social sciences or natural sciences, chemistry, physics or whatever, it’s nearly impossible to predict the impact of research when you do it,” says Professor Pall Thordarson, Director of the University of New South Wales RNA Institute and president-elect of the Royal Australian Chemical Institute.

“Something that might look completely obscure turns out sometimes to be the research that has the biggest pay-off.”

TODAY’S SCIENCE, TOMORROW’S TECH

It is that ambiguous pay-off that presents such a problem when it comes to funding.

Not only are science’s outcomes, by their very nature, uncertain, but they routinely take 20 or more years to materialise.

“It’s part of a continuum,” says Prof Calum Drummond, Deputy ViceChancellor of Research and Innovation at RMIT University. “It’s important to do fundamental research, to front-load the pipeline for societal benefit.

“In terms of the translation, you’re not always going to get immediate translation, but you may advance a body of knowledge and, ultimately, someone else might be able to use that advance or build on it to create new technologies, new products, new processes, down the line.”

Startup Quasar’s mission to produce satellite ground facilities has its roots in fundamental radio astronomy.

BUILDING POTENTIAL

In 1974, University of Melbourne Professor Richard Robson began building models. They were large, complex constructions made from coloured wooden balls and rods designed for undergraduate chemistry students, to illustrate the composition and bonds that form crystalline structures. Little could he know that his attempts to demonstrate inorganic particle composition would be the progenitor of an entire new branch of scientific discovery that underpins one of the most exciting commercial innovation prospects in contemporary Australian science.

Unless you’re a chemist, you may not have heard of MOFs. The acronym stands for “metal organic frameworks”: nanofabricated inorganic/organic hybrids with very high surface area ratios that give them some special and extremely useful properties. Today, MOFs are being used in everything from next-generation fuel research to targeted drug delivery and high-performance batteries.

Australian startup Airthena uses MOFs to draw CO2 from the air for industrial use. Researchers from RMIT are using MOFs to create next-generation gas masks. At Monash University they are using MOFs to convert seawater into potable drinking water using nothing but the power of the sun. None of this would have been possible without Robson’s

Prof Richard Robson pioneered a new field of chemistry.

original exploration of the potential of mapping, designing and redesigning crystalline structures.

TRAINING FOR EMERGING SKILLS

Dr Daniel Mansfield is a senior lecturer in the mathematics department at UNSW. After five years of blue-sky research into a hunch about some ancient stone tablets, he discovered evidence that the Babylonians used what we today think of as Pythagorean geometry in their land surveying — 1000 years before Pythagoras was even born.

Aside from the potential future usefulness of new ways of conceptualising maths, Mansfield argues there is strong educational value in discovery for its own sake.

“To me, the value of doing this kind of research is not that I can get a patent out of it. It’s because that stuff is awesome for inspiring the next generation of mathematicians,” he says.

“How are you going to inspire a roomful of 500 students or now, these days, a Zoom class of 500 students?” he says.

“How are you going to get them to tune in and actually listen to what you’re saying?”

And it’s those inspired minds who will be the ones feeding our research pipeline.

THE DOLLAR SIGN

University of Sydney graduate and former research fellow, Dr Ilana Feain, is an astrophysicist and commercialisation specialist with more than one startup

under her belt. She says a passion for science underpins all her commercial experience and success.

“Thinking back to my PhD, all I wanted to do was understand how galaxies formed, how stars formed, the interaction of black hole energy,” she says. “That got me out of bed in the mornings and nothing else mattered.”

Her drive to understand the fundamental principles of the universe eventually led her to commercial ventures as varied as medical imaging and satellite communication technology.

“We were able to do that off the back of some patents and innovations that would not have occurred had I not had that university background in astronomy imaging,” she says.

Feain was part of the group that spun off the startup Quasar. Their ambitious mission is to reimagine a technology originally designed for astronomy and space observation to produce satellite ground station facilities. This will play a huge role in managing the massive volume of satellites joining our sky to satisfy our seemingly endless appetites for data.

“Quasar is a perfect example of innovation and pure research for the sake of radio astronomy and understanding how galaxies form in the universe being translated into solving what is essentially a massive telecommunications bottleneck in satellite downlinks,” says Feain.

“Obviously, boundary conditions in place are important. But blue-sky research underpins almost everything.”

— Rachael Bolton MAR 2022

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outcomes

Stentrode has allowed paralysed people greater access to movement without the need for open brain surgery.

FUNDAMENTAL SCIENCE SUCCESS STORIES BRINGING NEW HOPE FOR PARALYSIS

In a two-year, world-first human trial run by the University of Melbourne, two people with paralysis have had a small device called Stentrode inserted under the skull at the top of their heads.

Associate Professor Tom Oxley, the inventor of Stentrode, was a University of Melbourne PhD student back in 2011 when he began exploring the idea of placing the electrodes in the brain via blood vessels through a vein in the neck. In 2012, he teamed up with colleague and biomedical engineer Associate Professor Nicholas Opie to develop and trial the device.

The device transmits signals to a computer, which translates the signals into commands like “click” and “drag”. The study participants can now search the internet, write emails and check their online banking.

REVOLUTIONISING LASER RESEARCH

Lasers were invented by US physicist Theodore Maiman in the 1960s and promptly picked up by mainstream media and James Bond movies as death rays. Fast-forward to today and they are used in multiple industries, medical practice and research. University of South Australia and the University of Adelaide are now collaborating with the Department of Defence’s Science and Technology Group (DST) to build a new type of high-powered laser that combines multiple smaller lasers, finetuning the manufacturing process so it is cheaper and more efficient.

DST says the ultrashort- and shortpulsed lasers are orders of magnitude more powerful than standard lasers and capable of vaporising or liquidising objects. “Our miniature laser technology and manufacturing processes are world-leading and will supercharge the DST’s laser system program,” says UniSA physicist Professor David Lancaster.

PERC SOLAR CELLS

In September 1983, University of New South Wales School of Photovoltaic and Renewable Energy Engineering Scientia Professor Martin Green’s lab set the first world record for silicon solar cell efficiency — 18%.

Later that year, in his report to the 8

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Australian National Energy Research, Development and Demonstration Program, Green suggested adding an extra layer on the back of a traditional cell architecture to improve light capture near the rear surface and optimise electron capture.

Known as PERC solar cells, this technology has revolutionised solar photovoltaics, raising efficiency and lowering the cost. These cells are now a commercial standard throughout the world, powering 85% of all new solar panel modules.

Green, who won the Global Energy Prize in 2018, spent three decades developing the idea with successive teams. PERC solar cells are now 40% efficient, with sales exceeding US$10 billion in 2017, and predicted to surpass US$1 trillion by 2040. It is estimated that they will save Australia at least $750 million in power production costs over the next decade.

NANOTECH IMAGING ADVANCES

Nanotechnology has its roots in the 1980s, when the new scanning tunnelling microscopes allowed scientists to see and manipulate individual atoms. For five years, La Trobe University’s Prof Brian Abbey and Dr Eugeniu Balaur have worked on modifying the surface of conventional microscope slides at the nanoscale.

The NanoMslide

The human eye can distinguish up to 10,000 different colours, but is far less sensitive to variations in intensity, which makes the addition of colours helpful when interpreting images. Typically, to identify cancer cells, medical imaging relies on staining or labelling cells to render them visible under the microscope, but it is still challenging to distinguish cancer cells from benign lesions.

Cancerous cells and healthy cells interact with light differently. Abbey and Balaur modified the microscope slide surfaces to make cancerous cells ‘light up’ with specific colours. The microscope slide developed from the research, NanoMslide, promises to revolutionise medical imaging.

“The key breakthrough came six years ago when we realised that, rather than working to improve microscopes, we could instead exploit recent breakthroughs in nanotechnology to revolutionise the humble microscope slide,” says Abbey.