Global Health Futures: Australian University Science issue #3

Issue 3, July 2020

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Research’s rapid response, p3

Training for industry success, p5 The vaccine frontline, p6

GLOBA L H EA LTH FUTU R ES

From detecting the virus in sewerage to tracing its origins, Australian university science’s rapid response to COVID-19 stunned the world and kept the virus in check

Developing new industries Training the future workforce | Leading in innovation

The people you turn to Science research at universities has a proud history in helping us to understand, protect against, and prevent many infectious diseases, from influenza to the viruses that cause some cancers. But university science goes far beyond medical innovation. In the 2020 pandemic, university science has quickly mobilised to model, trace and track the virus behind COVID-19. It has also focused research on cheaply manufacturing safety equipment, better directing our response to the pandemic through social distancing, improving our mental health research, assisting in the schools’ education transformation and rapidly sharing data.

Across the country, university science was able to draw on its teams and collaborations in the rush for a vaccine, with some strong candidates under development in Australia. Moreover, working with organisations such as the Australian Synchrotron, national supercomputing facilities, Australian industry and the CSIRO, potential vaccines are being scaled up and tested at a great level of detail.

As a repository of knowledge, networks, infrastructure and smart, agile people, university science has the capacity to address global challenges. University scientists work in a knowledge-sharing capacity that relies on scientists’ deep networks of collaboration and scholarship. Scientists share their data and knowledge nationally with each other and with industry, and also with international researchers, stakeholders in state and federal governments, schools and the wider public.

People trained by university science and working within the research sector are the people whose expertise will deliver on this global challenge because this is what they do. It’s the capacity to innovate in our university science that will bring us through this crisis.

Professor John Shine AC FRS PresAA President, Australian Academy of Science Garvan Institute of Medical Research

AUSTRALIAN UNIVERSITY SCIENCE

Exploring the achievements of university science in global health research.

Scientists across Australia have used their expertise to identify, understand and respond to the SARS-CoV-2 virus, helping the nation avoid catastrophe by modelling potential policy outcomes, developing personal protective equipment, finding treatments and working on a vaccine. Australian University

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Science highlights the collaborative work of the science community in this third edition, and profiles the roles graduates play in industry. To provide feedback or suggestions to the editors, subscribe to this publication or order additional copies, visit acds.edu.au/AustUniScience.

Cover Image: Jamie Kidston/ANU. Published July 2020

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. © 2020 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.

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Top: The UQ water testing lab. Middle: This scanning electron microscope image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells cultured in the lab.

Bottom: Prof Kevin Thomas at the Queensland Alliance for Environmental Health Sciences.

AUSTRALIA’S NARROW VICTORY “We have something that turned out to be my worst nightmare,” Dr Anthony Fauci, the top infectious disease specialist in the US, told biotechnology executives at a virtual conference in June. “In a period of four months, it has devastated the world.”

At the time, it was six months after the world learned that a new virus — SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) — had jumped to humans in Wuhan, China. More than 7.2 million people were known to be infected globally, and 411,000 had died of the disease it causes, COVID-19.

The numbers have since climbed astronomically, and it could easily have been a calamity for Australia. When the first four travellers from China tested positive on Jan 25 – one in Victoria and three in NSW – Australia ranked 4th in the world, just behind the US. Yet, when Fauci spoke, Australia ranked 67th with 7267 infected and more than 100 deaths, while the US led the world in number of infections and deaths.

Australia’s spectacular victory remains fragile. But it could not have been achieved without an army of highly skilled university researchers, who dropped everything to join the battle.

FROM TRACING DRUGS TO TRACKING A VIRUS

One such lightning collaboration was a proof-of-concept study to track COVID-19 in raw sewage as a potential early warning system.

In late March, University of Queensland’s (UQ) environmental health scientists Professors Kevin Thomas and Jochen Mueller approached CSIRO Land and Water’s environmental microbiology group to help accelerate the detection of specific gene fragments

from complex sewage samples.

Thomas says the open collaboration of the international scientific response to COVID-19 was immediate and immense.

“It is a sign that academic collaboration has changed for the better.”

“It’s been just remarkable,” agrees Dr Paul Bertsch, Science Director at CSIRO Land & Water in Brisbane.

“I’ve never seen collaboration at this scale and at this speed. Most collaborations become strong over time, but building relationships is usually done over many years, not weeks.”

Within three weeks, the team — expanded to include Japan’s Hokkaido University, the University of Notre Dame in the US and CSIRO Agriculture & Food — confirmed SARS-CoV-2 could be detected in sewage, finding virus gene fragments in untreated sewage from two wastewater treatment plants in Brisbane that service 600,000 residents.

The UQ researchers had been prompted by a Chinese study, published in Nature Medicine in late March, that found SARS-CoV-2 in rectal swabs of asymptomatic children who had nevertheless tested negative to nasal swabs.

Thomas’s Queensland Alliance for Environmental Health Sciences group was already monitoring wastewater to determine consumption and exposure to illicit drugs and pharmaceuticals for the Australian Criminal Intelligence Commission. Could they adapt their wastewater epidemiology to find SARS-CoV-2, they wondered?

They could, and the trial has shown that wastewater can be used to estimate how broadly the virus is circulating in the community, especially in those showing mild or no symptoms. “This is a major development that enables surveillance

Image: :NIAID-RML

The rapid response to COVID-19 by the country’s university science sector helped avert a disaster.

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Image: Microsoft

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species of bats and pangolins.

“The team also repurposed the workflow to assemble the whole genome of SARS-CoV-2, as the need of the hour was to understand the epidemiology of the disease,” she adds.

Such a high-resolution model of the genome would not only help understand the virus, but track its mutations. While the Houston lab, led

by Dr Aviva Presser Aiden, worked up virus samples, Kaur — now back in Perth — beta tested the data analysis scripts through the nearby Pawsey Supercomputing Centre to build reference genomes.

CHEAP, RAPID, EFFECTIVE TESTING

UWA’s Associate Professor Parwinder Kaur.

of the spread of the virus through Australian communities,” says Thomas.

Appearing in the journal Science of the Total Environment, it was the first published study of coronavirus surveillance in wastewater in the world.

“UQ and that group at CSIRO had never worked together, yet three weeks later they had a peer-reviewed paper,” says Bertsch. “That level of collaboration — not only across Australia, but globally — is really quite amazing around this crisis.”

RAPID RESEARCH RESPONSES

In January, just as the news of human-to-human transmission of SARS-CoV-2 broke, genome scientist Associate Professor Parwinder Kaur, from the University of Western 4

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Australia (UWA), was in Houston, Texas at the founding lab of the DNA Zoo. Kaur is the lead Australian partner of DNA Zoo, a global initiative with more than 60 collaborators in eight countries working to create reference genomes for threatened species across the tree of life.

Genomes are assembled using high-resolution 3D models showing the spatial distribution of DNA sequences relative to one another, a technology known as Hi-C that was originally designed to study how genomes fold inside the nucleus.

Importantly, it also allows a very detailed analysis of gene regulation.

As transmission of the virus accelerated, the DNA Zoo team decided to pivot into the effort, decoding the reservoir

With that data, they were able to develop a diagnostic test, which not only gives a yes/no answer to a patient swab saliva sample, but also the entire virus genome sequence.

In a bioRxiv pre-print paper, Kaur and her DNA Zoo colleagues report that the test accurately detects SARS-CoV-2 in 100 per cent of known samples, and is more than 95 per cent accurate in even small concentrations of virus (84 genome equivalents per millilitre) — better than the limits of detection for almost all diagnostic methods so far approved.

“It is highly sensitive — it detects very low amounts of the virus. And it’s really fast and very cheap,” she says. Using this method, one technician can process 192 samples at a cost of US$30 per patient, including data analysis time.

The partners have applied for emergency use authorisation with both the US Food and Drug Administration and Australia’s Therapeutic Goods Administration. But they’re not done.

“We’ve started using this to gather as much epidemiological information as we can, which can be shared with researchers on the front foot of vaccine development,” says Kaur.

“Right now, nobody’s waiting, it’s just an amazing pace. I mean, it’s in none of our KPIs to do this work, and I never thought I would work on a virus genome.

But it’s the virus pushing us to do it really, really fast.” — Wilson da Silva

profile

DEEP INSIGHTS INTO VIRUS PROTEINS

A globe-trotting career has taken Dr Cathy Yuen Yi Lee from Wollongong in New South Wales to the US and Europe.

A data scientist at Google Switzerland, Lee spent a large chunk of her career as a biostatistician tackling public health challenges. “In simple terms, it’s applying statistics to medical and health problems, and can really make a difference to public health policy,” she says.

After studying maths at the University of Wollongong, Lee took up a three-year biostatistics training program with the NSW Department of Health, which included a Masters of Biostatistics at the University of Sydney.

She followed up with a PhD at University of Technology, Sydney. This led her to an internship at Google Switzerland, several public health roles in Australia, a research fellowship at Harvard, and, finally, her current position at Google.

One of Lee’s projects involved studying risk factors for small and premature babies. Her analysis helped pinpoint priority areas for activities to prevent these babies becoming sick or dying – and fed into the NSW State Health Plan.

While she has landed some spectacular jobs, Lee says she didn’t start out with a detailed set of goals.

“My university training helped me discover what I wanted my career to be like,” she says.

As a beamline scientist at the Australian Synchrotron, Dr Eleanor Campbell is helping researchers unlock the structure of SARS-CoV-2.

When Australia’s pandemic lockdown started in March 2020, Campbell had only been in her role at ANSTO, the Australian Nuclear Science and Technology Organisation, for a few months.

“It was not a boring start!”

COVID-19 researchers were quickly given priority access to the Australian Synchrotron’s macromolecular X-ray crystallography. This allows them to investigate drug treatments by generating high-quality 3D models of the proteins that attach to the virus, as well as proteins the virus interacts with or builds inside the human body.

Campbell did a Bachelor of Chemistry and then a PhD at the Australian National University, accessing the Australian Synchrotron remotely for her research on proteins and enzymes. She took up an exciting research post at Cambridge University in the UK before landing a role at ANSTO as a beamline scientist.

Campbell says her university science training is “absolutely fundamental” to her work at the Australian Synchrotron as it built up her problem solving and critical thinking abilities.

“I couldn’t do my current role without it.”

— Nadine Cranenburgh

DR CATHY YUEN YI LEE

DR ELEANOR CAMPBELL

DIAGNOSING WITH LARGE-SCALE DATA

Bachelor of Mathematics (Adv Hons), University of Wollongong

Master of Biostatistics, University of Sydney

PhD (Mathematics), University of Technology, Sydney

Data Scientist, Google, Zurich, Switzerland

Bachelor of Chemistry (Hons) & PhD, ANU

Post-doctoral researcher, ANU

Post-doctoral researcher, University of Cambridge

Beamline scientist, ANSTO

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spotlight

THE VACCINE VANGUARD

Dr Daniel Watterson, Mrs Christina Henderson, Professor Paul Young, Associate Professor Keith Chappell, Professor Trent Munro.

Images: Glenn Hunt Photography

Australia’s long history of vaccine development earned us a position at the frontline in the race against COVID-19.

The expertise embedded in Australian university science ranges from complex modelling to trailblazing in genomic mapping, protein chemistry, bioinformatics and epidemiology.

So when COVID-19 spread across the globe, Australian scientists were equipped to better understand not just this virus, but also how we can protect ourselves in the future.

By June 2, the World Health Organization had identified 10 COVID-19 vaccines in clinical

Australia’s deep expertise in vaccine development meant science research was prepped to respond to COVID–19.

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evaluation and a further 123 vaccines in pre-clinical evaluation.

At the request of the Coalition for Epidemic Preparedness Innovations (CEPI), University of Queensland (UQ) scientists were some of the early responders, developing a rapid-response vaccine pipeline to reduce vaccine development from multiple years to a number of weeks.

Their vaccine shortcut uses ‘molecular clamp’ technology to trigger an immune response, research patented by UniQuest, UQ’s technology transfer company, and quickly pivoted to target COVID-19. The team is supported by University of Melbourne scientists who are running independent tests on the impact of the antibody response on the virus in cell culture.

UQ has since partnered with global biotech company CSL to manufacture the vaccine, with Phase 1 safety trials being conducted in Brisbane from early July.

If successful, vaccine production will be scaled up to an extraordinary 100 million doses towards the end of 2021.

“The partnership will enable the rapid development of the vaccine candidate through clinical trials, and by investing in large-scale manufacturing capacity now, we can reduce the time needed to deliver millions of doses of the UQ vaccine to those who need them most if it proves to be safe and effective,” says CEPI CEO Richard Hatchett.

A DEEP REPOSITORY OF KNOWLEDGE

Australia’s long history in vaccine research and the size of our research workforce are key parts of our arsenal, says microbiologist Professor James Paton, Director of the Research Centre for Infectious Diseases at University of Adelaide, and whose grandfather, Sir John Burton Cleland, was Principal Bacteriologist at the NSW Department of Health during the 1918–19 pandemic.

“Think of the human papillomavirus vaccine, Gardasil, for example, and medical technology such as Cochlear and Resmed — that’s a record of which Australian science can be justifiably proud,” he says.

With colleague Dr Mohammed Alsharifi, Paton is working on a new combination vaccine designed to simultaneously combat two deadly

respiratory diseases — influenza, caused by a virus, and pneumococcal disease, caused by a common bacterium. The combination formula would overcome the limitations of the existing vaccines used for both, and the pair hopes to be conducting human trials of the pneumococcal component within 12 months.

Paton points out that in both seasonal and pandemic respiratory disease contexts, people become far more vulnerable to additional infections.

Pneumococcus often ‘hangs around’ in our nose and throat without a problem – when our immune system is hammered by another illness, it can cause life-threatening bacterial pneumonia and sepsis.

Paton says the advantage of doing science research in the university sector is the cross-fertilisation of ideas.

“We have access to a wider range of facilities and a critical mass of people with expertise in different areas from our own,” he says.

SHOTGUN APPROACH LEADS TO RAPID RESEARCH OUTCOME

As the vaccine race kicked off, university scientists were already working to understand the evolution of the new threat. University of Sydney’s Professor Edward Holmes is an evolutionary biologist and virologist who co-authored one of the earliest descriptions of the SARS-CoV-2 virus, published in February 2020 in Nature and The Lancet.

His colleague, Dr John-Sebastian Eden, says their team researches “all aspects of viral evolution in animals and humans, even in insects”. They scan pathology samples from animals using total RNA sequencing to reveal the full spectrum of microbes present, a technique called Metatranscriptomic Shotgun Sequencing.

“Sequencing doesn’t just target specific microbes; we can recover any virus or organism that’s present in the sample,” says Eden. “These powerful sequencing techniques were done on lung wash samples from some of the earliest COVID-19 patients in China.”

In this shotgun approach, all RNA sequences present in a sample are extracted and the fragments are reconstructed using powerful computers.

Image: :Loren Elliott/Reuters

Left: UQ’s molecular clamp.

Right: COVID-19 testing during the first day of eased restrictions in Sydney.

The team then identifies the microbial life present by comparing these fragments to huge databases of known RNA, working with scientists at universities around the world to share their research via global genetic databases.

These hold billions of records of genetic sequences for organisms ranging from humans to bacteria, archaea and viruses – including more than 35,000 viral genomic sequences of the SARS-CoV-2 virus.

The unique facilities let scientists at Australian universities rapidly process data and keep tabs on the virus through molecular epidemiology, where samples of SARS-CoV-2 viral RNA from different patients are analysed and compared with others. That lets us track the virus’ spread in the community, and work out the country of origin for various instances of COVID-19 in Australia.

“These techniques are powerful,” says Eden. “We are also developing rapid turnaround for RNA sequencing so if an outbreak of a new disease of any kind happens, sometimes within hours, we can identify a novel organism.”

MODELLING THE SPREAD OF THE VIRUS

Mathematical biologist Professor James M ​ cCaw, from the University of Melbourne, is working with colleagues at the Doherty Institute on the modelling that guided the national cabinet to a solid public health response.

“We’ve been working for 15 years in this space to be ready for an event like this,” he says. “We provided advice to the government in mid-January, preparing scenarios of what could eventuate based on our epidemiological understanding at the time, before there were more than one or two cases in Australia and only

“IF AN OUTBREAK OF A NEW DISEASE OF ANY KIND HAPPENS, SOMETIMES WITHIN HOURS, WE CAN IDENTIFY A NOVEL ORGANISM.” a few hundred recorded in China.”

This modelling prompted early and decisive government action. “We’ve been prepared and the government took it seriously from the start,” he says.

Western Australia’s Chief Scientist, Professor Peter Klinken, says Australia was in a strong position to respond through a robust public health system and an excellent scientific community.

“Our public health experts have been really astute, and our politicians are listening to them,” he says. Klinken says that crisis situations can be plagued by groupthink — where no-one queries ideas — but this has been avoided by using innovative panels with a cross-section of expertise.

“They have reached out to the university sector and brought in epidemiologists, alongside experts in the mathematical modelling of diseases, engineers and virologists, all advising on how to plan – and that’s been invaluable.”

McCaw says that unmanaged, the virus has a reproduction number (R0) around 2.5. Unchecked, it would have killed tens of thousands of Australians.

“Through our public health response and the commitment of the Australian community, we avoided that disaster situation.” – Fran Molloy JULY 2020

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outcomes

SCIENCE INNOVATION AROUND COVID-19 BEYOND THE VIRUS University of South Australia’s A/Prof Colin Hall and Senior Research Fellow Dr Christiane Schulz.

SURVEYING MENTAL HEALTH

Professor Susan Rossell from Swinburne University is conducting a monthly survey of the mental health and wellbeing of Australians in the face of COVID-19, which will tell researchers what is causing most stress – finances, family or friends.

Dr Stan Steindl from the University of Queensland’s School of Psychology is co-lead on an international consortium looking at the psychological effects of COVID-19 in 18 countries, and how compassion can help reduce pandemic-related stress.

RESPONDING IN REGIONAL AREAS

Charles Sturt University established an internal fund for research projects that could achieve fast outcomes and improve our understanding of the impacts of COVID-19 on regional communities. Funded projects include research into the effects of chronic exercise on mitigating viral infection, and how culturally and linguistically diverse people in rural areas were impacted by racism related to COVID-19. Research led by Prof Jade Forwood investigating the structural binding relationships of virus proteins to novel therapeutic targets was also fast-tracked.

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TESTING PROTECTIVE EQUIPMENT

Adelaide packing company Detmold is manufacturing more than 20 million respirator and surgical masks per month for local and national markets. “In order to protect our vital hospital staff, face masks have to meet rigorous standards – they need to filter out bacteria, resist blood, withstand wear and tear, and yet still be easy to breathe through,” says Professor Karen Reynolds, Dean (Research) College of Science and Engineering, Flinders University.

Testing will take place at Flinders Tonsley site, and at the University of South Australia Future Industries Institute at Mawson Lakes.

“This both improves our capacity to respond to immediate demands due to COVID-19, and also provides new opportunities that will support the long-term viability of manufacturing businesses in South Australia,” says Professor Emily Hilder, who is Director of the UniSA Future Industries Institute.

MAKING MASKS

The University of Western Australia teamed up with the Harry Perkins Institute of Medical Research to manufacture 10,000 face shields for WA health workers. At the Australian National University, quantum physicist Dr John Debs mobilised the university’s Maker Space community to produce 17,000 plastic face shields, along with utility masks for general practitioners and other medical workers.

Macquarie Uni’s A/Prof Denis Bauer.

ANU physicist Dr John Debs.

HELPING HOME EDUCATION THRIVE

The Science Faculty at the University of Western Australia created a website with online learning resources to support teachers, students and parents.

Griffith University teaching staff set up weekly STEM challenges for students in Years 5–12 designed to be completed with materials and resources students had at home.

PROTECTING US IN THE FUTURE

Macquarie University’s Honorary Associate Professor Denis Bauer and colleagues at CSIRO used complex algorithms to compare genomes of more than 180 separate genetic sequences of the SARS-CoV-2 virus from around the world. The data shows

how the virus is mutating, and how different the individual isolates are from each other. The team has identified the most common virus strains, and therefore the best candidates to choose for testing vaccines. The team is now working with international collaborators to capture clinical data in a secure interoperable way to monitor emerging strains that might cause more severe disease.