MONASH UNIVERSITY

ARC National Competitive Grants · FY 2025 · 2025-01

A new mechanism of bacterial membrane defence against environmental stress. Bacterial membranes serve as a critical barrier against external stress and often undergo changes to adapt. This project focuses on investigating a novel adaptive mechanism related to the production of lipoamino acids, a unique class of amino acid-containing lipids. Using systems biology and computational and biophysical tools, this project aims to elucidate the biogenesis of lipoamino acids and their impact on bacterial membrane stability, as well as their interactions with membrane-targeting compounds. By uncovering these mechanisms, this research will greatly enhance our understanding of bacterial adaption to environmental stress and may inform the future design of new antibacterial approaches specifically targeting bacterial membranes. Field of research: 3107 - Microbiology Antimicrobial resistance has a significant socio-economic impact in Australia, posing serious challenges to health, agriculture, and the economy. Understanding how bacteria develop antibiotic resistance is crucial for addressing this pressing issue. This project focuses on investigating bacterial membranes, aiming to understand how bacteria alter their membrane composition in response to environmental changes and resist antibacterial compounds. Using cutting-edge technologies, including systems biology, and biophysical and computational tools, we will identify key factors, including genes and metabolites, involved in this process. These insights will inform the development of strategies to prevent the spread of antibiotic-resistant genes in the environment, which is crucial for preserving water and soil quality and safeguarding livestock health and food safety. Through strategic collaboration with established industry partners, our research has the potential to translate fundamental findings into commercial products. Ultimately, this project will contribute to improving environmental health and reducing economic burdens in Australia, aligning with the goals of Australia’s National Antimicrobial Resistance Strategy 2020 & beyond.

ARC National Competitive Grants · FY 2025 · 2025-01

Dissecting Nervous System Function – One Neuron at a Time. This project aims to investigate how the nervous system communicates to control behavior, cognition, and physiology. The project aims to map the function of communication molecules called neuropeptides in every neuron in a nervous system. This project expects to generate new knowledge in neuronal communication by employing innovative approaches in gene editing, animal behavior and physiology analysis. This study should provide significant benefits, such as training of Australian researchers in frontier technologies and acquisition of fundamental knowledge relating to brain function. This work may therefore stimulate future research in dissecting mechanisms that govern human neurological disorders and obesity. Field of research: 3105 - Genetics Brain function is essential for controlling behavior, cognition and metabolism. As such, defective signaling within the nervous system can cause psychological and metabolic disorders from epilepsy and autism to obesity. This proposed study aims to enhance Australia’s research capacity in the neuroscience field by enabling manipulation of the nervous system at an unprecedented level of specificity. This work may therefore identify future targets that are relevant to brain dysfunction. The potential economic, commercial, environmental, and social benefits are vast as better understanding of brain function is expected to have significant benefits for the health sector in the future. For example, the research findings will be of interest to pharmaceutical companies that design drugs for psychological and metabolic disorders. This project also expects to generate world-first tools to manipulate neuronal function at exquisite resolution and to expand our knowledge of how individual neurons control bodily functions. Further, this work will provide employment and exceptional training opportunities to Australian-based scientists and students in cutting-edge neuroscience techniques to expand Australian expertise. Beyond academia, our research outcomes will be promoted to the wider community through social media and media channels. Dissemination of our research will be aided by the Monash public relations office who are dedicated to assisting in communication of research discoveries.

ARC National Competitive Grants · FY 2025 · 2025-01

Are lymphatics a regulator of skeletal muscle growth, metabolism & renewal? This project aims to investigate the impact of factors secreted by or transported via lymphatics on skeletal muscle growth, metabolism and regeneration using cutting-edge imaging and lymph collection techniques. This project expects to generate new knowledge about the precise location, 3D structure and functions of skeletal muscle lymphatics, including as a critical regulator of skeletal muscle growth, metabolism and regeneration. This will provide downstream benefits to: 1) Society: identify factors to reduce loss in muscle mass/function with age or disuse that are associated with disability, frailty, falls, diabetes and death; 2) Sport: improving recovery and performance; 3) Agriculture: increasing meat quality and quantity per animal. Field of research: 3109 - Zoology The skeletal muscle accounts for ~40% of body mass and is essential for life - moving, breathing, eating and energy balance. New approaches to optimise skeletal muscle growth, repair and metabolism are critically required. The lymphatic system consists of lymph vessels and nodes that play key roles in fat absorption, immune function and fluid balance. Recently, we and others have revealed new lymphatic functions in controlling fat metabolism and heart growth and repair, however, the role of the lymphatic system in skeletal muscle is currently unknown. Using innovative imaging and physiological technologies, and in vitro/in vivo model systems, we aim to determine the precise location, 3D structure and functions of skeletal muscle. We will produce new knowledge on factors secreted and transported by lymphatics with exercise or muscle damage, and how these regulate skeletal muscle growth, metabolism and repair. By identifying new lymphatic targets for nutritional therapies or modulators to combat skeletal muscle dysfunction, our outcomes will have important benefits, leading to increased participation in sport, reduced frailty, and risk of hospitalization or death. We hope to identify factors that improve meat quality and quantity (primarily skeletal muscle) yielding economic and commercial benefits. Our new knowledge will be shared widely with scientific journals, conferences, press, community members and investors, and may be the subject of future patents and products.

ARC National Competitive Grants · FY 2025 · 2025-01

Deciphering the Intracellular Fate and Efficiency of mRNA Delivery. This project aims to improve the effectiveness of mRNA delivered using Lipid Nanoparticles (LNP). There is significant potential to improve mRNA potency through a deeper understanding of LNP interactions with cells. Our cutting edge approach combines innovative use of long read single cell sequencing with state-of-the-art nanoparticle targeting technology. The outcomes of the project will be: 1) quantifying intact and active mRNA delivered to cells 2) locating where mRNA is degraded 3) assessing cell behaviour after delivery of LNP/mRNA 4) engineering receptor-targeted LNPs that guide delivery of mRNA to where it is required This work will advance LNP delivery technology by maximising RNA expression and minimising off target effects. Field of research: 3106 - Industrial Biotechnology Lipid nanoparticles (LNP) that encapsulate an mRNA cargo have been integral to the global response to COVID-19. While immensely successful for emergency use during the pandemic, there are significant gaps in our understanding of how LNP delivery systems work. This project will identify and overcome the inefficiencies in LNP/mRNA delivery so we can develop the next generation of mRNA delivery systems. The economic potential of mRNA technology means there will be significant economic and commercial benefits. The ability to develop and manufacture the next generation of LNP/mRNA delivery systems in Australia aligns strongly with the government's Advanced Manufacturing goals. It also complements the investments made in establishing mRNA manufacturing facilities in Australia. Our team has strong links with local and international biotech companies and will continue our track record of translating fundamental scientific discoveries into commercially relevant products. Furthermore, we will use our award-winning virtual reality (VR) models to engage and inform the general public about our scientific advances. We have demonstrated that the VR platform is a simple and entertaining way to communicate complex scientific concepts to a broad audience.

ARC National Competitive Grants · FY 2025 · 2025-01

Hierarchical nanostructure effects on Nanoparticle-M Cell Interactions. This project aims to develop new design rules for advanced nanoparticle-based oral delivery systems targeting Microfold (M) cells in the gut, vital for efficient antigen transport. We will explore how nanoparticles' structures influence M cell interactions, focusing on transcytosis, differentiation, maturation, and enhancing mucosal immunity. Expected outcomes include innovative nanomaterials with specialized surface features tailored for M cell targeting, and fundamental knowledge into nano-mucosa interactions. This advancement promises to revolutionize oral vaccine delivery, offering substantial benefits in both the pharmaceutical and veterinary fields by improving vaccine efficacy and equitable access across diverse economic regions. Field of research: 3214 - Pharmacology and Pharmaceutical Sciences Nanotechnology holds significant potential for Australia's multibillion-dollar pharmaceutical and agricultural industry. Our project aims to use bio-mimicking nanomaterials to interact with Microfold (M) cells, essential gatekeepers in the gut that transport substances and regulate immunity. This research addresses a critical gap in understanding how these gut cells respond to changes in the surface nanostructure and chemistry of materials in mouse and chicken models and aims to develop new materials that specifically target and regulate M cells. This research will boost Australia's expertise in bioengineering and biotechnology, positioning the country as a leader in nanobiotechnology. The outcomes will benefit Australia socially, economically, and commercially by developing high-value materials and advances in the pharmaceutical and agricultural sectors. The new generation of M cell-targeting nanomaterials can be used in non-injectable delivery systems for nutrients, veterinary medicines, and vaccines, improving animal welfare and productivity cost-effectively, while ensuring better access across diverse economic regions. We will share our findings through peer-reviewed publications and public presentations. Licensing the intellectual property will guide future research directions. By working with industry partners, we aim to translate our research into commercial products and influence national and international practices through engagement with policymakers.

ARC National Competitive Grants · FY 2025 · 2025-01

Neural mechanisms driving dynamic responses to fatigue. Fatigue is pervasive, yet individuals vary widely in their response to it – some people are able to continue investing effort in spite of their fatigue, whereas others choose to rest. The neurobiological principles that govern when and why people decide to work versus rest remain poorly understood. This research will combine a novel behavioural paradigm with computational models of behaviour, pharmacological manipulations, functional neuroimaging and non-invasive brain stimulation to understand how we dynamically adapt our behaviour in response to the ebbs and flows of fatigue. Ultimately, this project will lead to a comprehensive neurobiological framework that is able to explain, predict and optimise behaviour as fatigue evolves over time. Field of research: 5202 - Biological Psychology Fatigue is unavoidable, and our productivity critically depends on how we adapt our behaviour in response. Continuing to work in spite of fatigue may lead to accidents, whereas too much rest may reduce efficiency. Importantly, the brain processes that guide our response to fatigue are poorly understood. This project will combine cutting-edge neuroscience tools to reveal the key brain structures and chemicals that determine how we respond to fatigue as it waxes and wanes. It will extend a partnership between neuroscience experts at Monash University and the University of Oxford, and provide an outstanding opportunity for early career researchers to engage in innovative interdisciplinary research. In particular, this project will grow capacity in a brain stimulation technique (transcranial ultrasound) that has the potential to revolutionise neuroscience research, but which is only just being adopted in Australia. The results will lead to biological models that allow us to predict when and why individuals choose to work vs rest, which will have significant implications for theoretical frameworks of fatigue. The knowledge generated from this project can be incorporated into future strategies and interventions to optimise our response to fatigue in the workplace, in the classroom, or on the sporting field. This may in turn benefit Australians economically and commercially by enhancing productivity, efficiency and learning, while minimising errors and accidents.

ARC National Competitive Grants · FY 2025 · 2025-01

Assessing recovery in threatened Australian amphibians and reptiles. This project aims to use a new methodology for determining the recovery potential of threatened species, and assessing the effectiveness of conservation actions. Using Australian reptiles and amphibians as a case study, this project expects to determine what is required to improve the conservation trajectory of Australia’s threatened species, and examine the effectiveness of current conservation policy. Expected outcomes of this project are the identification of species that are at elevated risk of extinction, and determining the conservation actions required to prevent these. This should provide significant benefits for improving conservation policy and planning in Australia, and the way that governments measure species recovery. Field of research: 4104 - Environmental Management Australia is one of the world’s biodiversity hotspots, but it is widely recognized that the health of its environments is declining. Australia has one of the highest extinction rates in the world, and thousands more species are threatened with extinction. The United Nation’s Convention on Biological Diversity (hereafter “the Convention”), which directs and informs international efforts on threatened species, has set targets to both prevent new extinctions, and ensure the recovery of threatened species. Although Australia’s conservation policy aims to contribute towards achieving these goals, it does not currently incorporate the key indicators that are required to do so. This project proposes to develop and trial a new, integrated approach to threatened species recovery, which incorporates the approved metrics under the Convention. The development of this approach will enable Australia to meet its international obligations under the Convention. The project will work directly with government to ensure that our results are relevant to conservation managers, and likely to be integrated into policy, providing a mechanism to improve the conservation, and recovery, of Australia’s unique biota. With predictions of the continued escalation of impacts from habitat destruction, invasive species and climate change, this project aims to provide an approach that will assist in ensuring Australia’s unique native biodiversity can survive and thrive through appropriate management.

ARC National Competitive Grants · FY 2025 · 2025-01

An investigation into metabolite-mediated immunity. This project aims to investigate how the immune system is modulated by metabolites, an emerging and key area of the life sciences. Presently, little is known about metabolite-mediated immunity, thereby representing a major knowledge gap. The project aims to combine mass spectrometry, structural and biochemical approaches to learn how metabolites are (i) presented by an antigen presenting molecule called MR1 (ii) how this leads to activation by specific T lymphocytes. Outcomes will significantly advance current understanding of the molecular basis underpinning metabolite-mediated immunity. Major benefits will include fundamental new knowledge about immunity that may ultimately be used by the biotechnology industry. Field of research: 3101 - Biochemistry and Cell Biology Metabolite-mediated immunity by T cells is emerging as a key area in the life sciences, being implicated in protective and unwanted immunity responses, and tissue repair. This proposal will explore the use of novel biochemical tools, combined with structural and mass spectrometry approaches to study how T cells of the immune system responds to metabolites. The national interest of this proposal lies in a) an advancement of basic knowledge in how metabolites modulate immune system function and b) the multi-disciplinary nature of the research proposal that will increase Australia’s research capacity within the life sciences via the training of a new generation of biochemists and immunologists with these skills. Further, this project will lead to patentable findings surrounding small molecule metabolites which will have direct implications for the biotechnology industry, where immunotherapies have the potential to treat many conditions relating to the function of the immune system. In addition to publication of results in generalist and immunology-based academic journals, the work will be disseminated to the public via media releases, social media and public lectures.

ARC National Competitive Grants · FY 2025 · 2025-01

Graphene for energy harvesting from the night sky. This project aims to establish the scientific foundations for new devices, based on the photothermoelectric effect in graphene, which generate energy from radiative cooling to the dark sky. The project will develop methods to strongly couple thermal radiation to graphene, understand the relevant mechanisms of electron heat flow in graphene, and build and measure the efficiency of graphene thermoradiative generators. The expected outcomes will be the benchmarking of this new technology with prospects for significantly higher efficiency, enabling new applications in space- and Earth-based power generation. The project will benefit Australia through intellectual property and new capacity for research in photovoltaics and quantum materials. Field of research: 5104 - Condensed Matter Physics Solar energy is important in addressing the societal challenge of net zero carbon emissions. Solar energy generation could be significantly enhanced by “thermoradiative” energy harvesting which exploits outgoing thermal radiation emitted (even at night) by warm objects exposed to the sky, while still utilizing incoming sunlight. However current thermoradiative generators harvest only a miniscule fraction of the available energy. This project aims to develop radically new device designs based on the unusual electronic properties of graphene (one atom-thick carbon), integrated with advanced nanostructures to efficiently release thermal radiation into the cold environment, potentially realising orders-of-magnitude efficiency improvements. The project will develop intellectual property, and manufacture and test prototype devices, falling within the National Science and Research Priorities of Energy and Advanced Manufacturing. Near-term benefits of efficient thermoradiative devices to government and industry will be new technology for power generation at night for autonomous vehicles and microsatellites, boosting Australian space and defence capability. The project will train researchers in forefront nano- and opto-electronics, essential in tomorrow’s energy technologies. Results will be promoted via public science websites aimed at a broad audience, and shared with industry and government stakeholders through workshops and site-visits to forge new partnerships for translation.

ARC National Competitive Grants · FY 2025 · 2025-01

Dissecting the implications of endosymbiont interactions for host fitness. This project aims to unravel the evolutionary implications of interactions between two endosymbionts - mitochondria and Wolbachia. All animals have mitochondria, and many carry the reproductive parasite Wolbachia. Each endosymbiont has profoundly shaped the evolutionary fitness of their hosts. Remarkably, however, each has been studied through different paradigms that ignored the capacity for the endosymbionts to directly interact to manipulate host function. Via an innovative approach, this project expects to generate new knowledge of the modes and mechanisms via which endosymbionts evolve, and the implications for their animal hosts. Expected benefits are results that directly inform the development of novel strategies for pest control. Field of research: 3104 - Evolutionary Biology Endosymbionts are living organisms that have evolved to live within the body or cells of another organism. Two of the most significant are mitochondria, the energy powerhouse of cells, and Wolbachia, a bacterium that can manipulate the reproductive and immune systems of their invertebrate hosts. Even though they reside side-by-side inside the cells of millions of species, they have only ever been studied separately. Incredibly, we have no knowledge of the capacity for these endosymbionts to interact with each other to shape the biology and evolution of their hosts. This project will redress this significant knowledge gap, opening a new frontier in the study of endosymbiosis. The project is expected to lead to significant national & international benefits. Wolbachia are key to biocontrol efforts; their introduction into mosquito populations blocks the transmission of mosquito-borne viruses, which would otherwise threaten the lives of millions of humans. By generating new insights into the implications to hosts of Wolbachia-mitochondrial interactions, the knowledge will have strong potential to shape development of more effective approaches to mosquito biocontrol. Project outcomes will be regularly discussed with Australian-leaders in Wolbachia-based biocontrol - the World Mosquito Program - and other stakeholders in biocontrol, such as CSIRO, through workshops and in-person meetings, thus enabling relevant insights to be incorporated into research & development pipelines.

ARC National Competitive Grants · FY 2025 · 2025-01

Many ways to die: unveiling the hidden diversity in ageing. This project aims to investigate how organ failure during ageing leads to cause of death, and why individuals die of different causes. Understanding how an individual’s genetic make-up interacts with influences from the environment, like diet, to alter the ultimate cause of death is lacking, but is crucial for advancing knowledge of why animals age and designing strategies to ameliorate health decline during aging. This project aims to expand ageing theory to include individual and environmental variation in cause of death. Benefits include enhanced understanding of the evolution of ageing and long-term improvements for the development of healthy ageing interventions. Field of research: 3104 - Evolutionary Biology Everyone wants to live a long and healthy life. However, the decline in organ function that happens with ageing and eventual death is inevitable. This has prompted researchers to explore why organisms age, and to devise a one-size-fits-all solution to delay this process. The problem with a one-size-fits-all approach is that individuals die of different causes and genetic makeup, sex, and environmental conditions can alter cause of death. Interventions to improve ageing outcomes that ignore this variation in cause of death are likely to be marginally beneficial, or even harmful, for many. This project aims to address this gap by identifying how and why the cause of death differs across individuals, sexes, and life experience using genetic model insects, fruit flies. This work has the potential to change how we think about ageing in all animals, enhancing Australia’s reputation in ageing research. While this project explores fundamental principles of ageing in insects, long-term applications include changing gerontology practice to centre personalised solutions for ageing. Our research will be communicated to a broader audience by engaging with our science communication teams to develop press releases for Australian and International media and through social media channels, reaching millions of people in a matter of seconds. This will make our findings accessible to the public, as well as to practitioners aiming to improve health outcomes in Australia’s ageing population.

ARC National Competitive Grants · FY 2025 · 2025-01

Discovering the sustainable size of cities. This project aims to theorise sustainable city sizes and develop a model to assess the impacts of impending high-speed rail on achieving these sizes across Australian cities. The project will generate new knowledge on city size dynamics, employing an innovative method that blends interdisciplinary approaches. Expected outcomes include a theory of sustainable city size, Australia’s first national level urban/transport model, a novel method informing high-speed rail planning, and a new approach to population distribution and urban growth management. The outcomes benefit Australia by reducing the burden of imbalanced population distribution (costing $200B/year) through a proactive planning of $200B investment in high-speed rail. Field of research: 3304 - Urban and Regional Planning Australia faces a $200B annual economic burden due to a mismatch in population distribution, leading to excess pollution, congestion, crime, and resource wastage. The population is predicted to double by 2066, worsening these issues. The Australian Government urges aligning the population with city capacity but struggles to find effective policy levers. This project aims to optimise the impending Australian high-speed rail network as a key policy tool to redistribute the population towards more sustainable city sizes. New methods are developed that go beyond conventional inter-census growth rates, employing a strategic approach to assess how new infrastructure might affect growth rates to determine sustainable city sizes. The project benefits Australia by ensuring the effectiveness of the $200B investment in high-speed rail, saving $5.5B annually in rental expenses, encouraging 44K more commuters to walk to work with health and environmental benefits, boosting community volunteering by 164K people, and saving millions annually by avoiding duplication in transport model development. It also provides new tools for pro-active population distribution management in Australia. The approach to impact builds on the CIs' extensive academic and policy networks. Project findings will be shared through policy and scientific advisory groups, experts involved in Delphi surveys and workshops, media releases, and policy briefs with local, state, and national governments for implementation.

ARC National Competitive Grants · FY 2025 · 2025-01

Are Brain-Wide Activity Patterns Governed by Simple Connectivity? This project will test key predictions of Neural Field Theory (NFT), an attempt to explain how patterns of neural activity are generated and propagate across the brain. It will use advanced optical technologies that afford high spatial and temporal resolution, important for critical tests of NFT. Among its aims is to investigate the potential to control brain-wide dynamics through resonance dictated by the brain’s geometry, one if the implications of NFT. It will lead to a better understanding of the roles of neural connections and brain geometry in generating activity patterns. The project may pave the way for future more reliable stimulation techniques, with implications for cognitive enhancement, healthy aging, and mental health. Field of research: 5202 - Biological Psychology All of our thoughts, sensations, actions, and emotions arise from various patterns of neural activity expressed across the brain through space and time. This project seeks to understand how these patterns are shaped by the anatomy of the brain by testing key predictions of a well-established mathematical model of brain-wide activity called Neural Field Theory (NFT). Specifically, the project aims to determine how the propagation of neural activity is fundamentally constrained by the brain's geometry (i.e., its size and shape) and how brain-wide activity can be amplified by periodic brain stimulation applied at the right location and frequency, triggering resonant responses (similar to tapping a pond repetitively to reinforce waves). Current evidence supporting NFT relies on relatively imprecise non-invasive imaging techniques in humans. This study will scrutinize the universality of NFT by examining species separated by over 87 million years of evolution: the mouse and the marmoset. This will be achieved through the application of state-of-the-art optical technologies for precise monitoring and control of brain-wide activity, available only in animal species. This study will deepen our understanding of the roles played by neural connections and brain geometry in shaping neural dynamics. It also holds the potential to establish collaborations with the Australian MedTech industry to develop robust stimulation devices for cognitive enhancement.

ARC National Competitive Grants · FY 2025 · 2025-01

Simple one pot bioconjugation using a novel molecular glue. Nanoparticle, polymer, protein and nucleic acid conjugation is critical for the fields of biosensing, synthetic biology, and drug delivery. However, most current bioconjugation techniques require chemical modification of biomolecules. This is costly, synthetically challenging, and can impair biological function. In this project, we will develop a family of proteins that act as molecular glue, allowing polymers, proteins, nucleic acids, and nanomaterials to be linked without the need to chemically alter the biomolecules. We will demonstrate the power of our novel conjugation technique by synthesising targeted nanoparticles, that are loaded with DNA and sensors that will allow us to quantify subcellular delivery of cargo. Field of research: 4003 - Biomedical Engineering This project will develop a simple, cheap and effective new to join biomolecules together. Biomolecule conjugation (joining two biomolecules, such as DNA, proteins or nanoparticles together) is essential for making better biosensors, more efficient drug delivery systems and develop cutting edge applications of synthetic biology. Current methods of bioconjugation are expensive, time consuming and can lower the activity of the biomolecules. Biomolecules are a high value manufactured items, and there is a significant potential to value add to Australia’s world leading expertise in the biotech sector. The project will expand Australia’s knowledge base in biotechnology through the training of interdisciplinary researchers. It will also develop intellectual property that will benefit the emerging Biotec and MedTec industries in Australia, and will provide significant economic, commercial and healthcare impact. We will use out strong links with local and global biotech companies (Starpharma, Patrys, Halozyme, Avidity) the help translate these fundamental discoveries into commercially relevant products.

ARC National Competitive Grants · FY 2025 · 2025-01

Inducing essential bacterial enzymes to self-destruct. Antimicrobial resistance is a looming crisis. Breakthrough cell biology is needed to identify new targets and new mechanisms of inhibition. This project aims to probe the susceptibility of bacteria to a novel “reaction-hijacking” mechanism, which has recently been discovered by our team. This work expects to catalogue targetable enzymes in bacteria and probe the inhibition mechanism using chemical, structural and cell biology approaches. Expected outcomes include the discovery of powerful chemical probes to study key metabolic enzymes in bacteria and a blueprint for the design of selective reaction-hijacking inhibitors. In the longer term, this work will underpin new therapeutic avenues for bacterial infections of humans and animals. Field of research: 3101 - Biochemistry and Cell Biology Australia’s National Antimicrobial Resistance Strategy recognises that an ever-increasing number of bacterial infections cannot be effectively treated due to the development of antimicrobial resistance (AMR). For example, ~40% of veterinary antibiotic treatments used in Australia work by blocking protein synthesis, but these treatments are at risk due to AMR, threatening Australia’s food security. We are exploring a new class of antibacterial inhibitors that target protein synthesis - in a new and unexpected way. We have discovered a class of molecules that blocks a key machinery in the protein synthesis pathway by “hijacking” a naturally occurring biochemical reaction in the cell. These molecules can induce the enzymes to generate their own inhibitors, leading to the death of the cell. We seek to understand the chemical determinants of this unusual "reaction hijacking" mechanism, so that we can design compounds that are more potent and specific for bacterial pathogens. This work will lead to new candidate antibiotics for treatment of animal diseases important to Australia. The project outcomes will be shared with industrial partners through meetings and conferences. In the longer term, this work could provide new routes to therapeutic interventions for bacterial infections of food animals and plants, and of humans. The work will generate new knowledge, build networks internationally and underpin new biotechnology applications to overcome global challenges in agriculture.

ARC National Competitive Grants · FY 2025 · 2025-01

As-printed titanium alloys with exceptional strain hardening. This project aims to make breakthrough developments of additively manufactured titanium alloys by utilising a new strain hardening mechanism. The project expects to generate new knowledge on how to effectively strengthen the commercial alloys’ microstructure and achieve superior damage tolerance. Expected outcomes of this project include an enhanced capacity to develop and commercialise titanium alloys with balanced mechanical performance that surpasses current versions. This should provide significant benefits, such as wide adoption of 3D-printed products in aerospace, transportation and energy industries and enhancing Australia’s international standing in cutting-edge research on advanced manufacturing. Field of research: 4014 - Manufacturing Engineering The project aims to develop innovative, high-strength 3D-printed titanium materials for use in industries such as aerospace, transportation, and energy. Current 3D-printed titanium alloys are prone to damage, limiting their application in critical components for airplanes, cars, and power plants. This project seeks to create more resilient titanium alloys that are less susceptible to breakage. The enhanced materials will significantly benefit Australian companies by enabling the production of safer, more efficient products through 3D printing. This technology will allow for time and cost savings, as well as the creation of intricate and customized designs. The outcomes of the project will advance the local manufacturing industry, leading to superior products, increased profitability, and fostering economic growth and innovation in Australia.

ARC National Competitive Grants · FY 2025 · 2025-01

Safeguarding posthumous digital data: understanding Australians’ views . This sociological project aims to understand Australians’ views on how posthumous data is or should be managed after people die or become incapacitated. The team expects to generate new knowledge of people’s views regarding the fate of personal data using community-based workshops, interviews, and a public forum. Expected outcomes of the project include a new concept of technological citizenship, enhanced international collaborations, and the training of researchers in a new field of vital importance to Australians. This should provide significant benefits such as deep understanding of the factors that shape people’s views on posthumous data that will assist estate planning, and evidence-based support for effective strategies and policies. Field of research: 4410 - Sociology Seventy percent of Australians are unaware of what happens to their digital data (e.g. online accounts, social media profiles, images, passwords) in the event of death or incapacity. Families are having to manage the digital data and assets of loved ones with few resources at the most difficult time of their lives. But unless appropriately managed and secured, this data has the potential to be stolen and used for identity theft, fraud, or to create fake images. The project will investigate Australians’ views on how posthumous digital data is and should be managed after people die or become permanently incapacitated. It will produce new evidence of people’s views and practices regarding posthumous data, using a series of stakeholder-oriented activities designed to ensure that practical strategies are aligned with community needs, priorities and values. The findings will assist the eSafety Commissioner, Services Australia, the ATO, and other organisations and companies that collect, store, and share data. They will provide the basis for policy and guidelines for government departments, patient groups, and businesses (e.g. legal services) on managing posthumous data, create tools to enable families to safeguard individuals’ data following their death or incapacity, and foster informed community debate on key issues. The outcomes will be widely communicated through public events, including live-streamed forums, podcasts, news articles, and open-access resources.

ARC National Competitive Grants · FY 2025 · 2025-01

A molecular investigation into marsupial T cell mediated immunity. Over ~ 400 million years, the immune system of vertebrates has constantly evolved to protect hosts from pathogens. Whilst much in-roads has been made in understanding immunity in humans and mice, there is a major knowledge gap in understanding how immunity operates in other mammalian species. This project aims to investigate T cell mediated immunity in marsupials and expects to generate new knowledge on a novel type of immune cell that is only found in marsupials. The expected outcomes of the project include a better understanding of the molecular correlates of immunity in marsupials. This should provide significant benefits for wildlife conservation in Australia. Field of research: 3101 - Biochemistry and Cell Biology The immune system has an essential role in health, through detecting threats in the environment and protecting against diseases. Most research on the immune system focuses on humans and mice, leaving a gap in our understanding on how the immune system works in other animals. This project will increase our knowledge of a novel type of immune cell that is found only in marsupials (e.g. kangaroos) and monotremes (e.g. platypuses). Understanding how these cells function and detect threats should lead to novel biotechnological developments. The outcomes of this project could therefore inform the development of treatments for animal diseases and protect Australian native animals threatened by disease (e.g. Tasmanian devils with facial tumour). This could ultimately fill a significant unmet need for conserving wildlife and provide a commercial and environmental benefit for Australia. The research outcomes will be promoted and shared with communities, non-governmental and governmental organisations (Wildlife conservation), and policy makers through a series of workshops, meetings, and seminars, enabling them to collaborate on implementation.

ARC National Competitive Grants · FY 2025 · 2025-01

X-ray Scatter Imaging: Vast Information with Minimal Radiation. Aims: This project aims to develop new X-ray imaging technology to provide detailed information about microstructures deep inside of objects using minimal X-ray exposure. Significance: This project expects to generate new knowledge in X-ray imaging using innovative methods that decode information created when X-rays scatter from small objects. Expected outcomes: Expected project outcomes include the development of high-resolution, three-dimensional imaging technology that gives vastly more information than today’s X-ray scanners, using safe radiation levels. Benefits: This should provide significant benefits in many industries, including improved sensitivity for disease diagnosis and detection of illicit substances in airport security. Field of research: 3202 - Clinical Sciences X-ray imaging is used everywhere from airport baggage handling to medical imaging. However, image contrast can be poor because it only utilises X-ray absorption properties. X-ray exposure can be harmful, causing illnesses including cancer, leukemia and infertility. Matter also scatters X-rays and this property can provide enormous amounts of information about an object, yet this information is not captured by conventional X-ray imaging. Scattering can reveal the size, shape, orientation and surface area of otherwise invisible microstructures. We aim to show that this vast information can be captured using new scatter-based X-ray imaging technology, and that scatter can help reduce radiation exposure by factors in the thousands. Scatter information usually requires specialised X-ray sources and optics to be detected, but we aim to demonstrate that scatter-based imaging can be achieved using table-top X-ray systems for real-time, low-dose imaging with micron-scale resolution. The potential benefits of this technology include enhanced detection of illicit substances in airport security scanners, and safer X-ray imaging with greater diagnostic capability. The vast applications of this technology mean it could also have great commercial benefits for developing new X-ray imaging scanners. Successful outcomes will be promoted to potential industry partners and clinicians, with the aim of translating this technology for industrial and medical use.

ARC National Competitive Grants · FY 2025 · 2025-01

Avant-Garde Kirchhoff's Laws Equivalent for Quantum Thermal Transistors . This project aims to formulate Kirchhoff's Current and Voltage Laws (KCL&KVL) equivalents tailored to quantum thermal transistors, which we pioneered. Drawing inspiration from the transformative impact of traditional KCL&KVL, which revolutionized the electronics industry, our endeavour seeks to extend these principles to the realm of quantum thermal transistors governed by the Schrödinger equation. This innovative approach will yield a unified set of KCL&KVL applicable to traditional and quantum thermal transistors, paving the way for advanced hybrid thermal control circuitry. The resulting software and design principles will catalyze advancements in electronics, including hybrid thermal management systems and chip-scale heat distributors. Field of research: 4008 - Electrical Engineering Transistors are electronic switching devices that are ubiquitous in modern society. As the technology matured, the observation that the number of transistors in a dense integrated circuit doubled every 18–24 months became known as Moor's law. For a long time, Moore's law predictions were true yearly, but not anymore. Traditional transistor technology has hit fundamental limits, mainly due to heat extraction issues. This project will address this challenge by developing new transistor technology that can increase the density of traditional transistors by providing an active thermal management pathway via thermotronic circuits powered by quantum thermal transistors. The proposed technology heavily depends on quantum effects, a critical technology the Australian government is actively targeting and promoting. This project will generate fundamental knowledge on analyzing transistor circuits built using both traditional transistors and quantum thermal transistors for the thermal management of conventional electronics. The resulting hybrid technology will be faster and more efficient. The resulting circuit laws, modified simulation software and the new hybrid thermotronic technology, will inform further research in Australia and help the Australian defence industry, universities and the global strategic microchip ecosystem. The associated intellectual property will enable licensing opportunities and commercialization pathways to boost critical manufacturing capability in Australia.

ARC National Competitive Grants · FY 2025 · 2025-01

National Security Exceptions in International Trade and Investment Treaties. This project aims to critically analyse national security exceptions in international trade and investment treaties, which states can invoke to justify treaty non-compliance. A recent proliferation of disputes reveals that some treaties' exceptions can be used as a guise for protectionism or other improper conduct, while others cannot be relied on when genuine security concerns arise. Expected outcomes include recommendations for negotiating, reforming and interpreting treaties that appropriately balance security concerns with liberalised trade and foreign investment protection. This will significantly benefit Australia by enabling it to take action to protect national security and by safeguarding the interests of Australian businesses. Field of research: 4803 - International and Comparative Law Governments are increasingly invoking national security to justify non-compliance with international trade and investment treaties, igniting geopolitical tensions and revealing problems with these treaties’ design. Many treaties permit states to rely on security as a guise for protectionism or other improper conduct with little or no judicial scrutiny, undermining the regime’s objective of global economic development. Yet, other treaties do not permit states to act in relation to contemporary security threats such as energy security and cybersecurity, undermining their sovereign right to protect public welfare. This project, the first of its kind worldwide, will develop strategies for treaty drafting that ensure that global trade and investment are not hindered by spurious invocations of security, while safeguarding states’ ability to respond to genuine security threats. The project will benefit Australia’s economic interests by ensuring that Australia can protect its security interests without legal liability and by minimising the risk that other states will improperly invoke security to justify measures harming Australian businesses operating abroad. More broadly, the project will benefit the international community by proposing durable solutions to remedy the regime’s problems. The project’s recommendations will be disseminated to policymakers in Australia and internationally (with the assistance of the United Nations) to maximise their adoption.

ARC National Competitive Grants · FY 2025 · 2025-01

Towards atomic scale magnetic field mapping and measurement. This project aims to map and measure magnetic fields at the fundamental atomic scale by building on new structure determination algorithms in electron microscopy and a new lens design enabling high resolution imaging of magnetic materials. This project expects to generate new knowledge about the structure of magnetic materials that will underpin next-generation technologies such as data storage and magnetic sensors. Expected outcomes of this project include new methods for characterising magnetic structures at smaller length scales than hitherto possible. This should benefit academic and industrial researchers for whom characterising magnetic structure is essential to improve capacity and energy efficiency of digital storage technologies. Field of research: 5104 - Condensed Matter Physics With Australians generating more digital data than ever, the need for increased data storage capacity with improved energy efficiency grows every year. To maintain pace with this ever-increasing need requires new technologies that maximise the use of the magnets that underpin this technology. Developing such technologies requires improved understanding and characterisation of magnetic structures on increasingly small length scales. This project seeks to address a research gap in characterising magnetic structures by developing imaging theory and analysis tools to measure and map magnetic fields down to the fundamental atomic scale. By training the next generation of researchers and strengthening collaborative links with researchers in the USA and Japan, this project will help keep Australia at the forefront of advanced materials characterisation. By developing our understanding of magnetic materials, this project will provide tools and insights that will potentially lead to environmental benefits by enabling new developments in power-efficient electronics, and economic benefits by enabling improvements in data storage capacity. The algorithms produced by this project will be promoted through open-source software and workshops to both academic and industrial researchers for whom characterising magnetic structure at this scale provides the insights necessary to build the next generation of digital data storage technologies to meet the ongoing needs of all Australians.

ARC National Competitive Grants · FY 2025 · 2025-01

Supply chain governance solutions for the gig economy. This project aims to identify ideal structures for business, independent workers and platforms, to ensure worker protection and service quality in the gig economy. Business depend on the gig economy for hiring flexibility and to lower costs. Gig work lacks the protection of other employment however with higher risks of worker injury or exploitation. Traditional buyer-supplier systems ignore independent workers and new buyer-supplier structures are needed to address a critical gap in labor governance. This Project uses an interdisciplinary approach to identify systems that achieve dual goals of worker protection and buyer flexibility. The Project's expected outcomes include better business oversight of gig work performance and protections. Field of research: 3509 - Transportation, Logistics and Supply Chains Gig-economy work is a rapidly growing form of labour. Gig-labour has been used increasingly by Australian business as it is more flexible, lower cost and scalable. Online platforms (e.g. Uber) organise labour for businesses by using 'self-employed' gig-workers. Gig-workers' contractor status, however, allows business and platforms to avoid labour protections provided to other forms of employment. As a result gig-work has less oversight, workers experience higher risks of injury, income insecurity, and discrimination, and service quality is lower. Firms and their supply chains can bridge the labour protections gap faced by gig-workers, however, especially given gig-work provides a growing range of services in firms' supply chains. The Project will investigate the role and perspectives of key stakeholders (business, platforms, workers, consumers) in gig-work labour protections. It seeks to identify supply chain solutions that maintain the flexibility and scalability of gig-based labour but also ensure minimum fair, safe working conditions. The Project improves Australian workers' access to sustainable gig-work which is a growing source of income for many. It also supports the economy by reducing gig-labour risks for industry which improves the resilience of Australia's supply chains. Project outcomes will inform recent government changes to the national employment system, and will be shared with industry, workers, and the international academic community.

ARC National Competitive Grants · FY 2025 · 2025-01

Thinning of nature . This research aims to understand how the declining abundance of life across foodwebs will affect the stability of ecosystems and the services they provide. Using pollination and seed dispersal foodwebs we will simulate and then test using real-world cases what happens to their properties and function when they lose individuals. The project expects to generate new knowledge about the resilience and vulnerability of ecosystems, using an innovative combination of methods. Expected outcomes include enhanced capacity to integrate these areas of expertise, and powerful models for predicting the consequences of environmental change. This should provide significant benefits including Australia achieving the goals of its Strategy for Nature. Field of research: 3103 - Ecology This project is about the problem that when individual plants and animals are lost from ecosystems, the services that they perform, such as pollination and seed dispersal, are also lost – impacting nature and agriculture. Such losses are expected under extreme climate change and land degradation. The research addresses the gap that the mass loss of individual plants and animals and the interactions between them have not yet been included in predictions of how climate change will affect nature and people, in Australia and elsewhere. The project aims to address this gap through analytical and computational innovation. The environmental benefits of this new research are being able to identify where in Australia this could happen, in which ecosystems, and to recognize its early signs so that government and land managers can intervene before the loss becomes irreversible. We will use our deep and well-established relationships with agencies responsible for nature in Australia and internationally to inform and guide the policy and management that underpins investment in nature to sustain people, agribusiness and tourism. We will build on our track record of experience on advisory committees, leading science-policy reports and volunteering to translate the outcomes and advance understanding of the research outcomes.

ARC National Competitive Grants · FY 2025 · 2025-01

Mind bender: how neuroactive drug pollution impacts wildlife cognition. This Project aims to investigate how widespread contamination by neuroactive drugs affects wildlife cognition and survival, and thus, the ecological communities they inhabit. It expects to generate new mechanistic insights into the emerging threat of pharmaceutical pollution across different scales of ecological complexity, from controlled laboratory experimentation to studies in the wild. Expected outcomes include new knowledge of direct relevance to chemical risk assessment and regulation. Findings should contribute significantly to understanding how wildlife respond to palpable environmental hazards, and enhance the evidence base for managing and securing biodiversity and vulnerable water resources—both in Australia and globally. Field of research: 3103 - Ecology Chemical pollution is among the fastest-growing and most insidious causes of global environmental change. Pharmaceuticals, when they enter waterways and accumulate in the brains of wildlife, are of particular concern. Despite this growing threat, no research has considered the impact on animals’ cognition, which governs all their behaviour in response to their surrounds. This Project uses ecologically important fish species to test how pharmaceutical contaminants affect the cognition and behaviour of wildlife, in a coordinated suite of world-first laboratory and field experiments. Beyond the clear advances in new science, it will fill a serious practice and policy vacuum with information for identifying and managing an emerging type of pollution that poses serious ecological, health, and economic concerns—as underscored by recent fears over the contamination of drinking water. Our findings will enable predictions of how pharmaceuticals can put at risk fragile ecosystems and the unique species they support, informing the secure management of freshwater resources. By training new researchers, this effort will expand Australia’s reputation and capacity for conserving precious natural assets both locally and globally. The Project will draw on our team’s consultative networks with community stakeholders as well as its strong links with national and international regulatory agencies, yielding translatable discoveries to inform risk assessment and regulation in this vital domain.