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A new way to fight drug-resistant bacteria

Professor Si Ming Man, John Curtin School of Medical Research, Australian National University, Canberra

Si Ming Man is tackling central questions of immunology: how do disease-fighting proteins produced by the immune system recognise pathogens, and how can these natural defence mechanisms be harnessed to fight infectious diseases?

The answers could lead to alternatives to over-used and increasingly ineffective antibiotics, providing new ways to combat multidrug-resistant microbes.

Disease-fighting proteins can recognise invading bacteria, setting in train an immune response. Understanding exactly how this process works, however, is a continuing challenge. 

Some 17 million people die each year from infectious diseases. Antibiotics are the first line of treatment but their overuse in hospitals and agriculture has resulted in an alarming rise in bacterial resistance. The United Nations estimates that by 2050 drug-resistant infections will kill 10 million people a year.

Si Ming aims to use his $1.25 million CSL Centenary Fellowship to study a particular family of disease-fighting immune system proteins known as guanylate-binding proteins (GBPs).

“The immune system is an incredible toolbox full of tricks, which we can learn from,” he says. “We now think the GBPs have a receptor similar to an antenna that can sense a pathogen once they invade our bodies.”

Four years ago, Si Ming made the exciting discovery that these proteins could attack E. coli bacteria. 

“They go and find the pathogen and break it apart, uncloaking it so the rest of the immune system can see it and destroy it,” he says.

That exciting breakthrough led to the hypothesis that the proteins could be harnessed as a disease-fighting system without the need to turn to antibiotics.

“The overall goal of the research is to find more and more of these disease-fighting proteins from our own immune system and harness their power to destroy all types of microbes, including bacteria and viruses,” he explains.

Si Ming’s work is ambitious because the family of GBPs is large. The CSL Centenary Fellowship allows him the space to give those ambitions full rein which could lead to lasting holistic solutions to the problem of multi-drug resistance.

“It provides continuous five-year support for young researchers like myself, which is incredibly important and my stage of my career,” he says. “That means that I can ask big questions, and train the next generation of young researchers.”


Photographs of Si Ming Man

2021 CSL Centenary Fellow Professor Si Ming Man (Photo credit: Science in Public)
2021 CSL Centenary Fellow Professor Si Ming Man (Photo credit: Science in Public)
2021 CSL Centenary Fellow Professor Si Ming Man at John Curtin School of Medical Research, ANU (Photo credit: Science in Public)

Video

Could Frizzled proteins lead to new cancer drugs?

Dr Alisa Glukhova, Walter and Eliza Hall Institute of Medical Research, Melbourne

Alisa Glukhova is investigating a fundamental cell communication system that guides the growth of embryos but, when it goes wrong, can contribute to cancer and other diseases.

By determining the structure and shape of the Frizzled protein, she hopes to create a path to new kinds of cancer drugs.

The cells in our body need to be told when to grow, what to become, when to multiply – even when to die.

But with close to 40 trillion cells in our bodies – and an unimaginable number of molecules in those cells – it is easy to see how things can go horribly wrong. And the result of those molecular misunderstandings can be catastrophic – a cascade of misinformation that can lead to the uncontrolled division of cells that is one of the hallmarks of cancer.

One of the key signalling systems in this process is the Wnt system. It’s so fundamental to life, it’s found in fruit flies, sponges, and humans.

We know very little about how Wnt signalling works – a gap in our knowledge Alisa hopes to close thanks to her $1.25 million CSL Centenary Fellowship.

That grant will support her work studying the signalling events surrounding Frizzled receptor proteins that lie on the surface of cells and act as tiny inboxes that receive messages from other cells.

We do know that many drugs can influence the Wnt signalling systems, including Frizzled receptors.

“We want to find new effective drugs that work with these receptors, or just to make ones we are already using work better,” Alisa says. But to do that we need to understand their shape and structure.

Alisa is bringing the latest technology to the task, using X-ray crystallography and cryo-electron microscopy. She will look at the structure of the proteins in a crystal form using synchrotron X-rays and she will visualise individual flash-frozen protein molecules using electron microscopy.

Alisa says that the five years of CSL Fellowship support will give her time to gain a fundamental understanding of the Wnt pathway that could then lead to the design of new classes of cancer drug.


Photographs of Alisa Glukhova

Portrait of 2021 CSL Centenary Fellow Dr Alisa Glukhova (Photo credit: Monash Photography Club)
Portrait of 2021 CSL Centenary Fellow Dr Alisa Glukhova (Photo credit: Monash Photography Club)
Portrait of 2021 CSL Centenary Fellow Dr Alisa Glukhova (Photo credit: Monash Photography Club)

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Filmmaker becomes co-author on paper published in top international journal, ‘Science’

Written and issued by Genepool

In an unusual turn of events, Melbourne based filmmaker Sonya Pemberton has become a co-author on a paper that has just been published in the top international journal Science.

The paper, ‘Global citizen deliberation on genome editing’ is calling for the creation of a global “citizens’ assembly”, made up of ordinary people who are tasked with considering the ethical and social impacts of this emerging science, in humans, animals and plants. The idea was born out of a film-research trip Sonya undertook almost two years ago.

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SUPPLEMENTARY MATERIAL – Why plumbers and teachers should have a say on designer babies and genetically enhanced potatoes

Extended quotes from selected authors

John Dryzek, Centenary Professor at the Centre for Deliberative Democracy and Global Governance at the University of Canberra’s Institute for Governance and Policy Analysis 

“A global citizens’ assembly will be a major step forward as the architecture of global governance of genome editing gets constructed. It will bring to bear the considered views of citizens of the world, who will be able to think about the content of public values and principles for regulation of the technology that could receive reflective acceptance in all parts of the world. 

“The is a big difference between what would be ideal and what is affordable. 100 would be good, 150 would be better, 200 better still. But note the participants are not there to represent countries, so we don’t actually need people from every country. They are there to represent the diversity of perspectives of the world’s peoples.

“This is not the United Nations General Assembly, where every country gets a vote no matter how big or small. For any realistic level of funding, we are going to have to do the best we can to maximise diversity of participants. It would be nice to undertake a global random selection process, but in practice we are going to have to compromise.

“For example, we can only handle about six languages in simultaneous translation before costs start getting prohibitive. If those six were (say) English, French, Spanish, Arabic, Chinese, and Hindi, that would cover over half the population of the world, and so still enable us to do a pretty good job in capturing diversity. 

“There is now vast experience with citizens’ assemblies and related processes in many countries, and none has ever yielded anything remotely like the madness of the mob. The fact that they are made up of citizens with no history of activism on an issue means they are good at reflecting upon the relative weight of different values and principles (think of how we trust juries in court cases to reach good judgements). Deliberation is a particularly good way (perhaps the very best way) to harness the wisdom of crowds, as it enables participants to piece together the different bits of information that they hold in constructive and considered fashion.

“We hope the GCA will get the attention of relevant international organisations such as the World Health Organisation and Food and Agriculture Organisation. But equally important is the contribution it will make to a more informed global conversation on genome editing, which will take effect via media coverage, social media, and the documentary series being produced in connection with the GCA.”

Dianne Nicol, distinguished professor of law at the University of Tasmania in Australia and director of the Centre for Law and Genetics.

“In the context of this project, my interest is in deeply analysing the ELSI of genome editing and examining how our our regulatory and governance arrangements need to be shaped to accommodate these ELSI. Community consultation is a crucial component of this. Given the global nature of modern genomic science, we clearly need to examine the ELSI from a global perspective. But we also need to recognise that there are particular local contexts.

I think that it is too simplistic to suggest that the purpose of the global assembly is to assist in building global consensus on acceptable uses of genome editing. This is complex technology, raising a host of ELSI. The issues to be discussed in this assembly are different from the types of issues examined in other forums of this nature (for example, whether same sex marriage should be legalised). I don’t think the goal of the citizens’ assembly should be to answer such questions as whether or not germline genome editing should be prohibited globally. Rather, it should be about better understanding community concerns and expectations regarding genome editing, understanding the norms and principles that underly these concerns and expectations, understanding what governance and regulatory arrangements are needed to address these concerns and expectations, understanding the factors that build and destroy community trust in the research, the researchers, the institutions and the regulators, understanding how to build trustworthy governance and regulatory arrangements, and so on.

The assembly is not intended to be representative of the global community. That would be impossible. Rather, the goal is for the assembly to attempt to reflect some of the diversity of the global population. It is not about hearing national voices but hearing community voices.

As noted above, the assembly is not intended to be representative, and any idea of this should be quashed, I think. It needs to be made clear that this is about diversity not representativeness. We will need to go through a very detailed recruitment process to ensure that we have as diverse a group as possible. But we will need to be very careful to avoid being seen as tokenistic – for example, we absolutely should not draw up a list of 100 desirable traits at the start and recruit to those traits.

“John and Simon have spent many years developing recruitment strategies for citizens’ deliberations to avoid the traps of representativeness and tokenism. Although this is their most ambitious project to date, I feel comfortable that they have the tools to bring together a group of 100 people who genuinely reflect some of the diversity of voices within the global population on genome editing.

The aim of the global assembly is not to provide an authoritative account of ‘this is what the world thinks about genome editing’. Rather, the global assembly will provide one account of community views on genome editing. The authoritativeness of this account lies in the robustness of the methodology – providing a form of public participation that has legitimacy, connectedness and reflexivity (as noted in the Science paper).

Pretty much every inquiry into genome editing calls for community consultation, but few if any provide concrete guidance on how this should be done. As noted in the Science paper, it is time to move beyond the rhetoric. The proposal for a global citizens’ assembly is a modest (?) step along the road to answering these calls. The outcomes from the citizens’ assembly will be disseminated broadly in a variety of formats.

“We will engage with relevant bodies during the course of the project and disseminate findings in ways that are meaningful and useful to them. It is hoped that they will make use of those findings because they have confidence in the robustness of the methodology and the features of legitimacy, connectedness and reflexivity.

“I’m not sure I have answered these questions in quite the way you need for the purpose of the press release. However, I don’t think we should oversimplify the challenges, nor oversell what the global assembly can achieve. I look forward to discussing these issues further on Thursday.”

Michael Burgess, philosopher in applied ethics at the University of British Columbia, Canada. 

“I think any focus on a consensus is a mistake. We are not trying to discover what it right or true, but how to live together, in the sense of a justified policy, when there is diversity of perspective and the issues are controversial. A global citizens’ assembly will consider the diversity of perspectives and the extent to which any decision affects the global population.

“Its validity and credibility will depend on the extent to which the full diversity of views has been introduced to the global assembly, and whether the deliberation gives careful attention and engages those perspectives as it considers policy options. The outcome will not be a policy with which everyone agrees, but one about which we can claim that the process to arrive at the recommendations was fair, inclusive and transparent.

“A deliberation requires participants to listen to each other, and the expert and stakeholder views presented to them as background for the deliberation. There is always a need to balance size with quality of deliberation. Too many, and there will be many participants who are not active participants. Too few and the full diversity of perspectives might not be considered.

“Having background materials and presentation from stakeholders introduces perspectives that might not be reflected by the participants. Participants sometimes bring up perspectives with which they are familiar, but that are not their own. The deliberation will need to be assessed for the inclusiveness, not only of the range of participants, but also for the active consideration of diverse perspectives. Also, if there are participants who do not actively engage, then that is a limitation as well. So while there is no magic about 100, it is an ambitious size for good quality deliberation while being likely to capture many of the diverse perspectives, particularly when supplemented by background materials and presentations.

“The weighting in deliberation is not the same a representative democracy. In any society, there are dominant voices, assumed ideologies and marginalized perspectives. Within a country or globally, it is crucial that deliberation does not merely reinforce the dominant and assumed perspectives, which are often mobilized by those with power, money and strong vested interests. The selection of participants in a deliberative forum like a citizens’ assembly needs to consider how to ensure that there is sufficient numbers of people with marginalized and non-dominant perspectives.

“In this sense, the selection of participants is intentionally corrective to a representative sample. Ideally, national deliberations would identify unique perspectives and then the global citizens’ assembly would attempt to be inclusive of those perspectives, regardless of home country.

“There are two common criticisms of deliberative engagement. One is that it is not a version of representative democracy and another is that the participants are not experts.

“The size of the deliberating group has been discussed above. A large number of participants who could not hear from each other or engage with the reasons provided in support of particular views is not much better than a survey that collects and aggregates uninformed and self-interested opinions. The point of introducing a public deliberative engagement process is to supplement the representation of the public by elected and appointed officials with what an informed public believes is in the public interests, having considered the diversity of public interests.

“The participants in a deliberation have expertise as members of public. We all do. This is the ability to consider benefits and risks and costs in particular decisions, and to make a decision. Experts develop an ability to provide estimates of the probability and magnitude of benefits and risks, often narrowly construed within their disciplinary field, or field of application. But when they tell policy makers and publics which of the benefits, risks or costs are most important, they are not acting out of their professional or disciplinary expertise.

“What is most important is not determined by a scientific or other expertise. People who believe that no risk to the global environment is tolerable are not so much rejecting the evidence of risk mitigation and benefits, but placing a high weight on the protection of the global environment. Citizens, often set up to think in binaries by media reporting, tend to decide who they identify with rather than consider the arguments. In a deliberation, participants are supported to individually and collectively consider both the advice of experts and the perspectives of people who assign importance differently for specific policies.

“These deliberations provide the basis and legitimacy for the citizens’ assembly’s recommendations, and it is up to the public and the policy makers to decide whether the process confers legitimacy and how to use that advice.

The global citizens; assembly, like all deliberative public engagements, provide advice. The only exceptions are when they are formed by legitimate authorities specifically to make a decision that will be implements, as in some forms of participatory budgeting.

“If the global citizens’ assembly is successful, that is if it is widely understood to be well informed, inclusive and civic minded in its recommendations, then it will stand independently as a set of recommendations that must be considered, and reasons given for deciding to form policy in ways that are contrary. More directly, if the citizens’ assembly’s recommendations are taken up by governments, NGOs and social movements, then they can utilize the credibility of the citizens’ assembly to motivate support for public policy that is responsive to the diverse interests of a global public.”

Baogang He, is Chair of International Studies at Australia’s Deakin University.

“A global citizen assembly will help to develop a moral and political regulation on genome editing experiment, and to develop and formulate a fairer distribution principle. Moreover, it will be a part of global civil society against ill use of genome editing for the interest of a few.

“100 is the rough figure, the number that is manageable in terms of logistic and operation. It can be increased a bit if all funding is secured. Ideally the more the better. However, the design a global citizen assembly is more about discourse presentation (on which John Dryzek wrote an important article) rather than country representation. It aims to represent a wide of opinions concerning moral and political principles regarding genome editing. The number of all countries to be represented is not an issue in the original design as the whole project is to develop global citizens’ perspective. 

“Related to the above, 100 participants are likely to represent major continents and major civilisations, in particular the sectors or stages of global genome editing process, like these countries who host experiments of genome and use the product of genome editing.

“Before global citizen deliberation, there will be more than 20 national deliberations in selected country, for example, in Shenzhen, China, where the first genome editing was experimented without governmental approval.

“The participants in each national deliberation will be randomly selected. I guess that there will be a further random selection process from these who participated in national deliberation. Through this double random selection process, the selected participants of about 100 citizens are to some extend representing global citizen perspectives. Moreover, there will be a deliberative process whereby the participants will engage with experts, international organisation regulators, business elites, and fellow citizens, and they will undertake opinion changes.

“These changed opinions after deliberation can be seem as authoritative and considered public opinion which can overcome the “wisdom of the crowd” or “madness of the mob”.

“The conclusion is a representation of global citizen’s perspective and their policy recommendation, that should be a part of global decision-process. Moreover, through national and global deliberation, it hopes that such an exercise can raise global citizen’s awareness of the life-matter issue facing mankind, and ultimately form a part of civil society’s monitoring force and mechanism against the abuse of genome editing.”

Sonya Pemberton, creative director of Genepool Productions, Melbourne, Australia.

“This is an experiment. It’s designed to allow lay people, non-experts from across the world, people off the street to consider the technology and its applications and then have a say in what they feel should happen next. It’s not about building consensus, it’s about listening and learning from the reactions, hopes and fears of a diverse group of people and seeing if, after deliberation, they can agree on a set of shared values, shared principles, that could underpin decisions around using this vital technology. 

“Up until now there has been no mechanism for people, across national and cultural borders, to engage in considering this complex issue, together. The great appeal of this project is that we will come to see how diverse the views may be, and we will discover if and how people can find common ground.

“The evidence from previous deliberative events is clear; when ordinary citizens are given the chance to gain credible information, the opportunity to exchange their ideas with a diverse group of people, and the time reflect on their views, citizens are willing and able to come up with recommendations to shared problems.  

“This is an opportunity to observe a remarkable process of public reasoning that may lead to shared practical outcomes.

“The end result is not to generate an authoritative position, rather it’s to see if it’s possible to determine a set of shared values and principles from which weighty decisions may be made.

“The important thing here is this is not a platform for exposing or arguing ones views; the scientists select for people that demonstrate genuine ability to engage with the issues and who commit to mutually respectful interaction. There is a shared commitment right at the start to the rules of engagement, and the focus of the event. The entire event is facilitated by experts in the deliberative process who will ensure all voices are heard, and that loud voices do not dominate.  It is about engendering trust and respect among participants, with shared purpose.

 “This is not about providing a speakers’ platform, rather a thinkers’ pool.”

Herve Chneiweiss, Director of UNESCO’s International Bioethics Committee and member of the WHO Expert Advisory Committee on the Governance of Human Genome Editing

Science and its applications, particularly in the field of emerging technology, must reconnect with the lay public and we absolutely need to fight against a divide between science and society. The simple existence of a debate organise with and for citizen should participate of this project and open debate with open citizen will allow to raise “commons” that will be translated into consensus.

Too many people would make a real deliberation impossible, not enough should make it inefficient. Our goal should be to be representative, thus it is not a Senate where each state would get one vote, whatever the number of its population. The “100” should represent the diversity of cultures and origins.

Our goal is to listen to musics poorly heard today. The diversity and the inclusivness of having people from around the world will make the sound of this original group so peculiar that it will be carefully listened.

“Such a global assembly will be so new and so representative that it will not be possible to take any decision without at least considering it. This does not mean that this jury will decide for every aspect of GE anywhere in the world. Local juridiction and international organisations are there to do so. But this jury will be so special that it will be difficult not to take its recommendations into consideration.”

National Science Week 2020 transforms during COVID-19

Media release from the Hon Karen Andrews MP, Minister for Industry, Science and Technology

This year’s National Science Week will embrace the problem-solving spirit of Australia’s science community, with even COVID-19 unable to stop celebrations beginning tomorrow.

More than 1,100 events are happening across Australia, many of them online, including Australia’s biggest satellite selfie, virtual tours of Great Southern Reef marine life and exploring wildlife in your own backyard for the Great Aussie BioQuest.

Launching National Science Week today, Minister for Industry, Science and Technology Karen Andrews said event organisers had shown great resourcefulness in rapidly adapting to the circumstances of the pandemic.

“As they say, necessity is the mother of invention and this year we’ve seen incredible inventiveness and a can-do attitude to ensure National Science Week can go ahead,” Minister Andrews said.

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ACT: A week of science at home

Media release from the Australian Capital Territory National Science Week coordinating committee

Discover more about local Canberra women in STEM, go on a science treasure hunt, hear about how video games and science connect, and experience the effects of climate change on our reefs through glass work and music. All this and more are part of National Science Week in the ACT.

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NSW: Science Week in NSW goes online

Media release from the office of the New South Wales Chief Scientist & Engineer and the NSW National Science Week coordinating committee

Due to COVID-19 restrictions, National Science Week takes an innovative twist this year, delivering a wide range of online events from 15-23 August 2020.

NSW Chief Scientist & Engineer Professor Hugh Durrant-Whyte said the state’s science community had risen to the challenges of lockdown: “Among hundreds of imaginative events and programs developed for the community to enjoy online are citizen science experiences, podcasts, innovation challenges, virtual tours, live-streamed panel discussions and science-themed, educational video games.”

“Scientists across NSW are taking the opportunity in Science Week to share their research, discuss why they became scientists and explain how their work helps to make our world a better place,” said Professor Durrant-Whyte.

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WA: How will you science in National Science Week 2020?

Media release for the Western Australian National Science Week coordinating committee

Drive a simulated remotely operated vehicle, go on a virtual Scouts camp, investigate how to bring animals back from extinction and explore the world beneath Earth’s blue surface without leaving your living room – it’s all part of National Science Week 2020.

Due to COVID-19, National Science Week 2020 has gone digital, exploring the inspiring world of science and technology from the Inspiring Australia WA website across the month of August. Some in-person events have been re-introduced due to COVID-19 restrictions lifting in Western Australia.

Watch WA’s Chief Scientist, Peter Klinken, introduce National Science Week 2020 here.

Dr Keal Byrne, Chair of the WA NSWk Coordinating Committee, said “Online and socially distanced, this year’s National Science Week is an amazing smorgasbord of innovative technologies and ideas that help make the world a better place.

“Anyone who is curious about the world around them should dive in to find out about environmental sustainability and entrepreneurship and the impact STEM has on our lives and our planet.”

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VIC: Possible Impossibles

Media release from Victoria’s National Science Week coordinating committee

The boundary between the probable and improbable blurs when National Science Week Victoria 2020 unleashes Possible Impossibles from August 15-23 – an online series of events and activities exploring the frontiers of possibility, and asking ‘What’s next for the human species?’.

Humans are a species of creative thinkers, problem solvers and ambitious dreamers. Together we have achieved the seemingly impossible, from curing diseases, extending the average lifespan, inventing air flight, harnessing the power of the Earth’s resources to connect people all over the world, to sending people into space. What does the future hold? Will we resurrect extinct species, figure out the hard problem of consciousness, and thrive on lab grown meat? Are time travel, invisibility, telepathy and suspended animation ultimately possible? Will climate change, ageing, waste, and food insecurity be oh-so 21st century?

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