UNIVERSITY OF MELBOURNE

ARC National Competitive Grants · FY 2024 · 2024-01

Innovative Strategies for Crafting Precision Kinase Inhibitors. Protein kinases are key regulators of cellular signaling, playing a pivotal role in diverse biological processes. However, most protein kinase inhibitors target a common binding site, leading to undesired effects on other kinases. This project aims to create highly selective protein kinase inhibitors by using structural biology to pinpoint unique interactions in the peptide-binding site. Using medicinal chemistry, we will enhance kinase selectivity of existing potent but non-selective inhibitors, and will validate their cellular pharmacology. Our innovative approach will be broadly applicable to diverse protein kinases of interest to academia and industry, and in the future will support the development of new drugs by Australian companies. Field of research: 3404 - Medicinal and Biomolecular Chemistry This project aims to create an innovative strategy for developing precision inhibitors that can selectively target a particular class of enzyme called protein kinases. Protein kinases are commercially significant enzymes that play an important role in regulating various biological processes, and many drugs act by selectively inhibiting their actions – but these drugs can also inhibit other enzymes, causing side effects. Through a collaboration with Australian company TianLi Biotechnology, this project will develop methods for developing kinase inhibitors that do not interfere with other enzymes, and then translate the developed methods into the Australian biotechnology sector. This will equip Australian researchers and firms with an effective approach for developing kinase inhibitors with fewer side-effects, which in the long term could have potential as drugs. This strategy for creating precision inhibitors will provide a robust foundation for a globally competitive Australian biotechnology sector, particularly in the field of pharmaceuticals targeting protein kinases.

ARC National Competitive Grants · FY 2024 · 2024-01

THE BASAL MELTING OF ANTARCTIC ICE SHELVES . The project aims to determine the mechanisms that govern melting of Antarctic ice shelves into the ocean. Faster basal melting of ice shelves in the warming ocean is contributing to loss of grounded ice from Antarctica and increased glacier speeds, and melting is projected to become a larger contribution to future global sea level rise. Using unique laboratory experiments, turbulence-resolving computation and theoretical analysis the project will evaluate the roles of meltwater, ocean currents, internal wave breaking and water exchanges between the continental shelf and sub-ice cavities. The results will assist our understanding of measurements made in Antarctica and more reliable predictions of sea level rise. Field of research: 3708 - Oceanography Over the past decade melting of the Antarctic and Greenland ice sheets has contributed to around 40% of global sea level rises. Much of this melting is occurring in West Antarctica and is thought to be caused by warmer and saltier water from the Southern Ocean pushing its way into shallow waters on the Antarctic continental shelf and interacting with the ice shelves. To better plan for future sea level rises it is very important to know how fast the ice sheets are melting and how much the melted ice will contribute to sea levels. As it is very difficult to measure flow properties under the ice shelves and the way the melting occurs, current predictions about the melting rate are not precise. This project will develop world-leading basic knowledge of the physics of ice shelf melting in Antarctic seawater using experiments and simulations. Expensive measurements made under the Antarctic ice shelves will be more effectively interpreted. New ocean observations and climate models with improved melting schemes will allow better predictions to be made about changes in the Antarctic ice sheets. New knowledge will be widely disseminated to relevant scientific and government agencies through articles and media. Accurate predictions are critical for policy makers across the globe and are particularly important for Australia where our coastlines are long and highly populated. Supporting Australia prepare for sea changes due to climate change is an important environmental benefit.

ARC National Competitive Grants · FY 2024 · 2024-01

Defining pathways that control T cell lifespan for long-term immunity. This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defence against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identification of the genes and processes that control lifespan. This should provide significant benefits in the basic knowledge of how longevity of immunity is regulated. This understanding will be useful for future immunotherapeutic applications, such as veterinary or human vaccines requiring maximal duration of immunity Field of research: 3204 - Immunology In vertebrates, the immune system is used to fight infections (e.g. by viruses or parasites). A key property is that certain immune cells ‘remember’ an infection so can quickly act if reinfection occurs. This is the basis of how vaccines work. As shown with COVID-19 vaccines, this immune memory may not last forever. We have discovered that how long immunity lasts is affected by properties of the original exposure (e.g. the type of infection or vaccine). This project will investigate certain immune cells that give long-term immunity to define properties affecting their lifespan. This knowledge could enable us to extend the length of cellular memory and thus of immune protection. Beyond this application, findings could lead to development of vaccines that give longer protection, potentially improving the health of humans, livestock and pets. Future research may also enable shortening of harmful immune responses, potentially helping people and animals with autoimmune diseases (e.g. diabetes). The findings apply to a broad range of contexts and could bring economic benefits to the Australian biotechnology sector. Training and mentoring the early- and mid-career project members will develop future Australian scientific leaders and build links to established international networks. Our work with a NZ biotech startup illustrates a pathway for translating outcomes. The findings will be communicated through the media and social media, including activities on the Day of Immunology.

ARC National Competitive Grants · FY 2024 · 2024-01

Co-designing Innovations in Digital Storytelling with Older Adults. This project aims to investigate how emerging technologies can be leveraged to provide innovative ways for older adults to create and share their life stories to foster social wellbeing. Later life can be a time of considerable change, leaving people feeling disconnected from the people, places, and life events that are important to them. Autobiographical storytelling can help create links with one's past, but little is known about how technologies such as digital games and virtual reality can be used to enable older adults to share stories about their lives in a way that supports ongoing social interactions. This project is expected to co-design new forms of digital storytelling to improve social wellbeing of older adults. Field of research: 4608 - Human-Centred Computing Ageing well has social, health, cultural and economic benefits for Australia. Ageing well means not just staying healthy, but also staying socially engaged. Yet, social wellbeing can be threatened by the changes associated with ageing, such as retirement, bereavement, and declining health and mobility. For many older people, sharing autobiographical stories can be a valuable way to communicate their identities as people who have lived rich and full lives. Storytelling through short digital videos that capture life events and experiences, is one strategy for sharing older adults’ stories. The Australian Association of Gerontology nominated digital storytelling as its “hot topic” for 2023, but noted that digital storytelling is currently underutilised. Also, current forms of digital storytelling support one-way communication only, missing any ongoing social interactions between the storyteller and their audience. Our project will identify how new technologies can be used to create digital stories that are interactive and playful. It will enhance the social connectedness and wellbeing of older Australians, contributing to ageing well by supporting their social and cultural participation. We will share guidelines for using new forms of digital stories in workshops with seniors’ groups and care providers. This will promote one of the goals of Australia’s new cultural policy: that all people can be storytellers, and that all audiences can experience their stories.

ARC National Competitive Grants · FY 2024 · 2024-01

Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quality of life for older Australians and address the physical realities of an ageing workforce. Benefits extend to enhancing workplace safety and productivity, improving farming efficiencies for livestock and aquaculture industries, and training emerging leaders in the biological sciences. Field of research: 3109 - Zoology Skeletal muscle’s ability to adapt to life’s challenges decreases throughout the lifespan and represents a critical challenge for the world’s ageing population. To understand how muscle adaptation is regulated at a molecular and cellular level, and the implications for muscle function, this project aims to interrogate how muscles respond to growth and endurance signals using innovative gene technologies and molecular physiology tools in different animals. The project seeks to address some of the most intriguing and unresolved questions in muscle biology relevant to development and ageing, and to generate knowledge to improve quality of life for all Australians, while addressing the physical realities of an ageing workforce. Further benefits extend to enhancing workplace safety and productivity, improving farming efficiencies for livestock and aquaculture industries, and facilitating the mentoring of emerging leaders in the biological sciences. The research outcomes have far-reaching impact and will be communicated broadly through the broadcast and print media, news and business channels, social media and community platforms.

ARC National Competitive Grants · FY 2024 · 2024-01

Unravelling Efficient Nucleic Acid Delivery Using Multilayer Nanoparticles. Developing smarter nanoparticles is critical for maximising the potential of biological therapeutics such as nucleic acids. Currently, the efficiency of nanoparticle delivery remains low due to the inability of carriers to migrate different biological regions. The aim of this project is to develop responsive polymer nanoparticles that can more effectively migrate cell barriers by a two-staged release based on the combination of different self-immolative polymers. This project will allow the development of design rules for understanding how nanoparticle structure can be optimised to improve nucleic acid delivery. This work will have important benefits such as developing new nanotechnology industry and skilled graduates for Australia. Field of research: 3403 - Macromolecular and Materials Chemistry Nanoparticles are small structures that can be designed to protect drugs, only releasing cargo in a target site. The properties of these materials make them ideal for creating new and innovative products, including application for diagnosis and treatment of human diseases. Nanoparticles have been approved for use in humans and are increasingly common, as we have seen in recent times with the nanoparticle carriers used to manage the COVID virus. However, many challenges are faced in the process of nanoparticles being able to deliver fragile cargo to our body cells. This project develops new smart nanoparticles that can more effectively deliver biological therapeutics such as the nucleic acids to their site of action, by releasing active components in multiple stages. This research will have major economic and commercial benefits through the development of new nanoparticle technology that will generate industry investment and commercialisation opportunities. Partnerships with government and industry bodies will ensure that the research findings are fully explored, and commercial opportunities realised. This work is expected to have long-term impacts on improving treatment efficacy, preventing diseases and contributing to people living healthier and longer lives.

ARC National Competitive Grants · FY 2024 · 2024-01

Dissecting bacterial signal transduction. Bacteria have feelings. They sense and respond to changes using proteins called two-component signalling systems (TCSS). These comprise a sensor which activates a DNA binding protein in response to specific cues (signals). Using state-of-the-art genetic techniques and a synthetic biology approach, this research aims to reveal for the first time how these complex bacterial TCSS networks interact. The outcomes will be a fundamental, new understanding of how bacteria sense and respond to environmental signals; a deep dive into how bacteria feel. This knowledge will be the basis for innovative approaches to harness bacteria in biotech such as vaccine production, biofuels, or clever therapeutic interventions to stop bacterial infections. Field of research: 3107 - Microbiology Biotech encompasses technologies across agriculture, marine, health and environment that use bacterial processes to develop products. These processes in bacteria are controlled by molecular sensing systems. We need to deeply understand how these sensing systems work so we can harness the full biotech potential of bacteria to efficiently make high-value biologics such as enzymes, antibiotics, biofuels, animal and human vaccines, among other products. This project directly addresses that need and will generate fundamental new knowledge on how bacteria detect and respond to their environments by revealing for the first time the full complexity of these sensing systems. The research findings will have direct implications across the many biotech industries that rely on cornerstone industrial bacterial processes such as fermentations to make enzymes, vaccines and foods. This research will directly inform bioengineering of bacteria to make high-value biologics. This in turn has the potential to create substantial national economic wealth in a global biotech market worth over $1000 billion and growing, aligning strongly with a pillar of Australian government long-term biotech strategic direction. We anticipate that the knowledge gained from these studies will be communicated widely through public presentations, media press releases, social media posts, formal publication in peer-reviewed scientific journals and incorporation into university undergraduate teaching curricula.

ARC National Competitive Grants · FY 2024 · 2024-01

Engineering Functional Antimicrobial Polypeptide Surfaces. Antimicrobial coatings are vital in preventing bacterial contamination but a versatile solution does not exist. Structurally nanoengineered antimicrobial peptide polymers (SNAPPs) were recently developed to fight multidrug-resistant bacteria. To expand their application into antimicrobial coatings across a range of surfaces, a simple and universal coating strategy is needed. By developing phenolic-functionalised SNAPPs, this project aims to exploit the adhesive nature of metal–phenolic materials to rapidly coat diverse surfaces, including stainless steel and textiles. The expected outcome is the generation of antimicrobial polypeptide surfaces, which will have benefits in food safety, medical implant technology and advanced textiles. Field of research: 4016 - Materials Engineering With widespread use of antibiotics in society, bacteria are increasingly developing antibiotic resistance. Known as superbugs, these resistant bacteria are challenging our healthcare to find new medicines and new ways to prevent infection. Prevention of infection is a global challenge beyond healthcare and medicine as bacteria can live on many surfaces including those in the food supply chain and on textiles. We will develop an emerging class of antimicrobial nanomaterials against multidrug-resistant bacteria using a simple and universal surface coating strategy. This new generation of antimicrobial nanomaterials will be anchored to surfaces by combining nanoengineered antimicrobial peptide polymers. We will promote our results through peer-reviewed publications and public presentations. Licensing of intellectual property will inform future research directions. Applications of these antimicrobial polypeptide materials can be used as coatings on medical devices, textiles and food packaging. This research will benefit Australia socially, economically, commercially and environmentally through the development of high-value materials and advances across multiple sectors. It will improve healthcare, reduce food spoilage and increase food shelf life. By tackling antimicrobial resistance impacting humans, foods, animals and the environment, this research aligns with the research priority area set in Australia’s National Antimicrobial Resistance Strategy 2020 & Beyond.

ARC National Competitive Grants · FY 2024 · 2024-01

Optimising disease surveillance to support decision-making. COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis and 2) translate these findings into the blueprint for a next-generation infectious disease surveillance system for Australia. We will use a simulation-evaluation approach, coupling methods from infectious disease modelling with those from information theory optimal design. Outcomes will enable more tailored and effective pandemic response. Field of research: 4901 - Applied Mathematics The COVID-19 pandemic exposed major shortcomings in infectious disease surveillance systems in Australia and globally. Surveillance data and associated analytics played a critical role during COVID-19: reducing disease spread and saving lives. However, it became clear that traditional disease surveillance systems are not designed to support real-time data analytics that provide critical evidence for decision-making. This project aims to develop the blueprint for a next-generation infectious disease surveillance system for Australia. A range of novel surveillance methods will be devised and implemented in an advanced modelling and simulation platform. Using methods from statistical information theory and optimisation, we will then determine the surveillance methods that provide the most useful data for decision-making. A diverse stakeholder panel will be consulted throughout the project to help guide our findings into a realisable blueprint. Implementing this blueprint would enable a more tailored, adaptive, and effective response to a range of pandemic threats in Australia— reducing their health, social and economic impacts, thereby maximising community wellbeing. The project team’s networks and continuing leadership roles in providing epidemic advice to government will ensure the research results reach policymakers and public health authorities for implementation.

ARC National Competitive Grants · FY 2024 · 2024-01

Replicating the cartilage micromechanical environment. Through a novel, image-guided mechanical evaluation of cell- and tissue-level remodelling, this project aims to unlock new insights into the complex mechanical microenvironment of cartilage and directly influence new strategies in tissue engineering. The research will reveal contributions of cells and extracellular matrix components to mechanical integrity over time. It will build a world-first strain map of the cartilage microenvironment and quantification of dynamic structural remodelling that occurs, providing key targets to improve tissue engineering strategies. The project will also drive innovation in micromechanical testing technology, deliver functional solutions in mechanobiology and advance materials for biological integration. Field of research: 4003 - Biomedical Engineering Cells are continuously exposed to mechanical loads as we move about. They contain mechanosensors that respond to these stresses; for example, cartilage responds by remodelling to suit the loads it is experiencing. Different stresses (e.g. compression or fluid pressure) trigger different responses. Understanding the link between mechanical stimuli and the cellular response in cartilage is key to understanding joint biomechanics. In this project, we will develop a 3D model to analyse how cartilage cells respond to loads. Rather than elastic gel (which rebounds), our model mimics cartilage by supporting the cells in a medium akin to solid sand (solid but with fluid). Our unique hardware will allow image-guided micromechanical evaluation of the types of load cells are feeling and how they respond over time. The findings will unlock new insights into the complex mechanical microenvironment of cartilage and directly influence new strategies in tissue engineering. This project could lead to efficient and robust methods to determine the suitability of diverse materials for future use that integrate mechanically with a biological environment. Strong links with industry will encourage the use of our findings in real-world applications in biotech, agriculture and healthcare (e.g. to improve longevity of existing implant technologies). The wellbeing of many Australians would benefit from better treatment of musculoskeletal burdens, which could also save billions in healthcare costs.

ARC National Competitive Grants · FY 2024 · 2024-01

Causal Knowledge-Empowered Adaptive Federated Learning. Federated learning tools are a promising framework for collaborative machine learning (ML) that also maintain data privacy; however, their ability to model heterogeneous data remains a key challenge. This project aims to develop a new learning scheme for coordinated training of ML models that successfully bridges variable data distributions. The framework proposed will be the first globally that can use causal knowledge to 1) handle data heterogeneity across devices and 2) address the real-world challenges when only a subset of devices have labelled data. Expected outcomes and benefits include the theoretical underpinnings and algorithms of causality-based collaborative training of ML models while better preserving the users’ data privacy. Field of research: 4611 - Machine Learning Artificial Intelligence (AI) and associated Machine learning (ML) systems are an integral part of our daily lives. ML models have traditionally been trained from a centralised dataset, but with data now increasingly distributed on network of devices (such as mobile phones, wearables, and Internet of Things sensors), an adaptive new training architecture is needed. Responding to this, our ARC Discovery Project will pioneer collaborative training of ML models on a network of different computing devices – delivering coordinated learning without data sharing. The research innovates in its fundamental theory, in its design of new learning parameters to address variable data quality across devices (including labelled and unlabelled data), and in its enhanced features for privacy protection. Developments from this project will promote Australia’s competitiveness in securing a future share of the massive markets for artificial intelligence applications on mobile phones, wearables and other smart technologies. In this context, our research targets efficient collaborative training of ML systems on these devices to enhance their functionality, while preserving the users’ data privacy. New software generated from the project will be released under open-source licence; articles produced for magazines, trade journals and researchers; and patenting explored for potential commercialisation and licensing opportunities for Australia targeting both local and global markets.

ARC National Competitive Grants · FY 2024 · 2024-01

Deciphering the immune complexity that orchestrates T cell activation. The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional level. We have developed new and sophisticated experimental models that will allow us to systematically dissect and unfold the complexity of the adaptive immune system and address this critical knowledge gap. Expected outcomes will critically advance our general understanding of a fundamental biological principle. Field of research: 3204 - Immunology A mammal’s immune system can effectively distinguish if a foreign substance is safe, like food, or potentially harmful like a pathogen. While complex networks within our body are required for this vital function, it is still unclear how this works. Taking advantage of animal models specifically developed to address this crucial knowledge gap, we will dissect and unfold the complexity of the immune system to identify how organisms regulate such ‘friend-foe’ discrimination. The outcomes of this study will critically advance our general understanding of a fundamental principle relevant to all mammals, which includes livestock and endangered native animals, whose health is of critical value to agriculture and the tourism industries of Australia. Moreover, outcomes will fill critical knowledge gaps and generate new intellectual property that will afford excellent opportunities for research and development including the generation of new experimental models, which will be distributed to further amplify research output and impact. New knowledge generated by the project and the high-level international training of students will increase the competitiveness of the biotechnology sector in Australia and generate intellectual property that can be further developed by Australian Biotechnology companies into novel products for veterinary and health services to increase productivity. Critically, outcomes will be shared via social and print media to be accessible to the general public.

ARC National Competitive Grants · FY 2024 · 2024-01

Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Drosophila, and cell-based models. Findings will provide basic knowledge about this mysterious gene and uncover how it modulates an essential pathway in embryonic development. This research is expected to impact knowledge generation, health, and well-being. Field of research: 3105 - Genetics Each of us are born with organs that form a stereotypical shape and size. This is controlled by genes or molecules that signal to organs as they are forming, providing instructions for how to grow and organise. Because organs are highly sensitive to changes in these signals, animals have evolved ways to subtly increase or decrease signalling, providing exquisite control. Whilst we understand the major components of signalling, we do not fully understand how they are controlled. Recently, we have discovered a new gene essential for signalling control and the patterning of organs. Intriguingly, this gene is found in diverse species, such as animals, plants, and algae. This suggests it is an ancient gene and may teach us about evolution. The project will use multiple animal models to investigate the function and evolution of this gene. It will advance our biological knowledge of organ formation and generate new scientific methods and tools in the field of biology. The project will employ Australian researchers in highly skilled and specialised research, training them for jobs in academia, Industry, and the health sector. Beyond this project, it may also provide improved technology for stem cell-based therapies and diagnostics. Outcomes from this work include the generation of new knowledge, to be published in international journals, reported in press releases and via social media, and presented at both national & international conferences.

ARC National Competitive Grants · FY 2024 · 2024-01

Bridging the meaning gap: A computational approach to semantic variation. This project aims to create and validate a new class of large language models that capture and partially explain semantic variation between people. We will (1) measure nuanced differences in word meaning and linguistic experience across individuals; (2) develop computational models that incorporate this variation; and (3) evaluate the extent to which the models capture behavioural and cognitive differences related to political affiliation, gender, and culture. This will advance our understanding of the nature and origin of individual differences as well as improve the calibration of AI systems for under-represented groups. These advances will support eventual applied outcomes in health, domestic security, and resilience to misinformation. Field of research: 5204 - Cognitive and Computational Psychology Recent advances in artificial intelligence programs like ChatGPT have enabled the nuances of language to be modelled at scale, and offer potentially enormous technological and applied benefits. However, these models often fail to transparently capture the variation in meaning that occurs between individuals, especially those from groups (like Australians) that were under-represented in the text that the models were trained on. Our project aims to fill this significant gap. We will build on existing work to develop a novel computational model of meaning for specific individuals and groups, and then evaluate how these meaning differences are related to people's differences in cognition, behaviour, background, and linguistic environment. Besides improving our understanding of how experience shapes how we think, the project will help to address known biases in artificial intelligence (AI) so that it is better calibrated for Australians as a whole as well as some of the diverse communities that exist within our country. The new tailored models we develop will be useful for identifying and fighting targeted misinformation, improving intergroup understanding, and creating more targeted health interventions. Our dissemination strategy makes use of our extensive networks with other scientists, our established platforms for communicating with the general public, and our existing connections to end-users in defence, cybersecurity, and heath.

ARC National Competitive Grants · FY 2024 · 2024-01

National research impact policies: Uncovering the ‘value’ in evaluation. This project aims to identify the conceptions of value that underpin national research impact policies and to examine the consequences for research activities, outputs, and outcomes. By studying four countries with different national policy approaches to research impact, it is expected that significant new knowledge about the role of research in society will be produced. Expected outcomes include a framework that links markers of value (i.e. what counts as valuable research) to research policy and assessment principles. Expected benefits include policy learnings to improve how research is evaluated in Australia, thereby enhancing the alignment between what is valued by those who fund research, those who produce it, and those who use it. Field of research: 4407 - Policy and Administration The Australian government makes a significant investment in research, science and innovation ($11.8b in 2021-22). This investment is meant to empower Australia to be globally competitive as a knowledge economy. Australia’s research system is highly productive, ranked tenth globally in citations. However, its capacity to translate research into outcomes that benefit Australian society and the wider world is less demonstrated. This project investigates four countries with distinct policies on the societal benefit of research – Australia, the United Kingdom, Germany and South Africa. It will generate knowledge on the nature and effects of these policies and their implementation. Through strategic engagement with the Research Excellence Branch of the Australian Research Council and other stakeholders, this project’s findings will be used, via stakeholder forums, roundtables and targeted reports, to inform research policy and assessment practice. This project will provide value to the Australian government, research policymakers, and the research sector by analysing and developing new strategies on translating research into societal benefit. This will help: the government (via evidence on return on research investment), research policymakers (via evidence on planning, monitoring and evaluating societal benefit), researchers and administrators (via strategies for creating, reporting and promoting wider benefit) and the public (via clarity on the value of research for society).

ARC National Competitive Grants · FY 2024 · 2024-01

Midbrain hunger signalling modifies decision making under conflict. Decision-making is one of the most important and fundamental biological processes executed by the mammalian brain. Environmental threats and physiological pressures, such as hunger, can influence decision-making processes skewing the risk/reward ratio, yet how the brain integrates these conflicting goals to determine action selection is unknown. This project aims to investigate brain chemistry and circuitry controlling decision making under conflict using a multidisciplinary approach combining behaviour, pharmacogenetics, and sophisticated molecular and functional profiling. The expected outcomes will advance theories regarding the neural organisation and computation of decision making under conflict. Field of research: 5202 - Biological Psychology Everyday decision making is often accompanied by conflict - whether we make the most appropriate decision or not can be influenced by both internal and external factors. This project aims to understand how the brain integrates signals from the external environment and internal signals from within the body, such as hunger, to make decisions when conflicted. Using innovative methods, we will characterise and alter activity of the brain to gain insight into how this information is incorporated in mice. This knowledge is critical for many industries in Australia, with the potential to inform primary food production industries (agriculture, fisheries), which could lead to improved growth rates, health & well-being, and survival of animals; ultimately enhancing economic outcomes. Further, such new knowledge may influence advertising (how hunger status guides purchasing decisions) and education (optimal environments to facilitate learning) with our findings shared broadly through media, social media and community engagement. This research will make important contributions to our fundamental understanding of how the brain computes risk/reward decisions in different environmental conditions, while training the next generation of scientists in state-of-the-art neuroscience techniques. Long-term it may also have implications for the health and pharmaceutical industries, laying the foundation for new treatments for neuropsychiatric disorders characterised by impaired decision making.

ARC National Competitive Grants · FY 2024 · 2024-01

Predatory protists: natural weapons for soil-borne pathogen control. This project aims to understand the mechanistic interactions of predatory protists and fungal pathogens and develop innovative biotechnologies using the protists to suppress soil-borne pathogens. By directly preying on fungal pathogens or activating plant-beneficial bacteria to combat them, the soil predatory protists will be identified, cultivated and utilised to improve disease management. Expected outcomes of this project will include a mechanistic understanding of the contribution of protists to pathogen suppression and an innovative, protist-based disease management tool. The novel technologies developed in this project have potentials to benefit Australian agriculture and land management. Field of research: 4106 - Soil Sciences Soil-borne fungal pathogens represent a significant threat to global agricultural production and food security, and are projected to increasingly impact crop yields under future climatic scenarios. This project aims to address a significant knowledge gap in the use of predatory protists, which are major predators of soil microbes, to effectively control soil-borne fungal pathogens. The project will generate new knowledge about the major functional groups of protists that can suppress soil-borne pathogens, and develop high-throughput methods for cultivating plant-beneficial protists and creating synthetic protist communities to enhance disease suppression. The use of predatory protists as a disease management tool has the potential to reduce dependence on chemical fungicides and improve the economic viability of Australian agriculture. The outcomes of this project thus will have significant economic and environmental benefits to the Australian community. This project will also contribute to enhancing Australia’s international reputation as a leader in sustainable agriculture practices. This framework developed in this project will serve as a model for developing agricultural biotechnology tools that are based on trophic control within microbial food webs, and can drive sustainable agriculture to feed our rapidly growing population.

ARC National Competitive Grants · FY 2024 · 2024-01

Shuffle algebras and vertex models. Shuffle algebras are important new mathematical structures that offer a new approaches and techniques to solve outstanding open problems in a variety of branches of mathematics, including mathematical physics, algebraic geometry and combinatorics. This project proposes to find solutions to key open problems using connections between shuffle algebras and integrable lattice models. The expected outcomes include (i) a new framework of shuffle algebra techniques to solve challenging research problems in mathematical physics and statistical mechanics, (ii) practical and computationally feasible constructions of shuffle algebras using vertex models, (iii) solutions to unresolved spectral problems of open quantum systems. Field of research: 4902 - Mathematical Physics The development of new, advanced mathematical techniques provides the modern toolkit that is essential to progress much innovation in science and engineering. This project focuses on a type of newly discovered mathematical structure, called shuffle algebra, that can be used to analyse models in quantum mechanics and statistical physics. The further development and deeper understanding of these structures will help to address complex research challenges in physics, engineering and computer science. Solving those challenges will provide important long-term commercial and economic benefits for Australia, informing new advances in quantum computing, complex engineering and material science that can be utilised by Australian business, industry and finance. The project will also help train a mathematically sophisticated workforce, prized by the finance, resources, information technology and manufacturing industries, with economic and social benefits for Australia. The mathematical tools and findings developed in the project will be made freely available to a wide industrial, computing and academic network, so that these techniques can be used to explore many different applications.

ARC National Competitive Grants · FY 2024 · 2024-01

An adaptive surface for improved modelling of rough wall bounded turbulence. This project aims to improve the prediction of drag where fluid flows over rough surfaces. This is a significant problem, with the uncertainty in drag penalty prediction for shipping alone exceeding ten billion dollars annually. The societal importance of these flows demands action, yet novel approaches must be sought to efficiently explore the wide range of roughness types encountered in practice. An adaptive surface is proposed, where a roughness configuration can be dialled in at the press of a button, to rapidly converge on improved models. A key outcome of this project will be improved predictive models of drag for rough wall flows. Benefits will include improved efficiencies and reduced emissions across a wide range of industries. Field of research: 4012 - Fluid Mechanics and Thermal Engineering The flow of air or water over rough surfaces occurs in many processes, both natural and man-made. Examples are fouled ship hulls, transport of water or gas through pipes, and the atmosphere flowing over complex terrain. These processes profoundly influence Australian lives, dictating the energy efficiency of engineering systems, and affecting the accuracy of weather and climate models. Despite this prevalence, and over a century of effort, our ability to predict these flows is far from complete. This is due to the vast range of rough surfaces and coverages involved (from sparse patches of barnacles on ship hulls, all the way to crops and forests in atmospheric flows). Currently available data cover only a small range of these scenarios and many questions remain unanswered. To redress this issue, we will build a novel tool (a computer-controlled, adaptive surface) that will allow us to rapidly test an unprecedented range of relevant surfaces. We will communicate our findings to our peers and through our networks of industry partners and regulatory bodies. This step change in our ability to predict these flows will have far-reaching benefits for Australia. Improved efficiencies in engineering systems will reduce emissions and save energy, costs and time. Society will gain from better-informed regulations, for example on ship fouling, with environmental benefits. Refined models of atmospheric and oceanographic flows will enable improved weather and climate forecasts.

ARC National Competitive Grants · FY 2024 · 2024-01

The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene. Field of research: 3105 - Genetics Animals need a blood supply for nutrient and waste exchange to both develop and support life. This need is met by a network of blood vessels throughout the body. Vessels form via sprouting and growth prompted by proteins called growth factors. Growth factors signal to blood vessels, instructing them to multiply and remodel to form new vessels. Growth factors are incredibly potent in stimulating vessel growth and, as such, there are accessory proteins to modulate their potency, ensuring vessels grow in the right place at the right time. The project focuses on a newly identified modulator of growth factor potency that has been shown to be essential for blood vessels to form correctly. We currently don’t understand how it functions so are restricted in our ability to use this molecule to promote vessel growth for the improvement of health and well-being, and potentially the growth of livestock. The project will generate new knowledge about how this modulator functions. It will employ and train Australian researchers in highly skilled and specialised research, improving human capital and these individuals’ ability to secure high-paid jobs in academia, industry, and the health sector. We anticipate new intellectual property may also be generated by this research. Outcomes from this work will be published in open access international journals, reported in press releases, promoted on social media and presented at both national & international conferences.

ARC National Competitive Grants · FY 2024 · 2024-01

Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity. Field of research: 3101 - Biochemistry and Cell Biology T cells are the body’s fighter planes that protect humans and animals from infection and tumours by taking down the invaders (pathogenic viruses). To date, the activation and function of T cells has only been studied in the context of a single invader but the reality is that mammals can harbour more than one infection at any given time, perhaps in sequence or concurrently. Our current understanding of how T cells cope with multiple invaders is limited. This project will study activation and function of T cells when exposed simultaneously to two unrelated invaders. This proposal will develop new knowledge on how the body’s fighter planes are activated, transported, primed for attack and stored for rapid response to future invasions. Some of the long term benefits include commercial development of new human and animal vaccines and rational design of novel regimens for T cell immunotherapies, relevant for infectious diseases, cancers and future pandemic threats. This project will provide training in cutting-edge techniques to study the immune system for the next generation to ensure Australia remains the leading country in the field of the national priority, Health. Outcomes from this project will be communicated to the general public via news-articles, public lectures and social media channels.

ARC National Competitive Grants · FY 2024 · 2024-01

Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essential target genes that drive lymphatic development. The project expects to generate fundamental knowledge in vascular signalling, transcription and the control of vascular network growth and expansion. Outcomes may provide significant benefits in new approaches in stem cell biology, tissue engineering and regenerative biology. Field of research: 3105 - Genetics In vertebrate animals, a network of lymphatic vessels (thin walled, bloodless vasculature) underpins healthy tissue growth and function. We know these vessels play several key roles in normal tissue function and inflammation. However, there are fundamental gaps in our understanding of the specific underlying processes that control lymphatic vessel formation and function. This project will expand knowledge in a new area of cellular signalling in the control of lymphatic vessel formation, growth and function. Unlocking new knowledge in the control of lymphatic vessel formation and function has potential to lead to new innovations in organ and tissue engineering, tissue repair and regenerative biology. In the future, this work may generate innovative approaches in biotechnology and pharmaceuticals. Longer-term outcomes may help people keep working and participating in social activities as they age through new tissue repair and future biotechnology applications. The project will build cutting-edge research capacity in Australia through training scientists in world-class molecular and cellular biology of vasculature and vascular signalling. We will promote our findings through publication in journals with suitable open access policies, presentations at leading international conferences, press releases and through social media.

ARC National Competitive Grants · FY 2024 · 2024-01

A statistical decision theory of cognitive capacity. This project aims to investigate the limited capacity of the human cognitive system to form representations of the things in the world around us and to make decisions about them in real time. Its goal is to provide an integrated theory of cognitive capacity based on the statistical properties of cognitive representations and the decision processes that act on them. Its expected outcome will be a unified metric for cognitive capacity that will allow us to quantify how cognitive load affects the speed and accuracy of decision making. It will benefit the design and evaluation of high workload real-time decision systems and will contribute to the selection and training of users of such systems. Field of research: 5204 - Cognitive and Computational Psychology A brightly-illuminated digital billboard changes abruptly as you pass it. It is distracting but is it dangerous? Digital billboards are one facet of a modern “attention economy” aimed at capturing and exploiting attention, whose architects understand that human cognitive capacity – that is, the attention, memory, and decision-making processes that form mental representations of events in the world and translate perception into action – is a limited resource that can be exploited economically. More generally, people must interact with complex designed systems that place demands on their cognitive capacity and in which information overload can lead to decision errors that may have serious consequences. At present we have no general metric to measure and predict the cognitive demands of the environments in which we place people. The aim of this project is to develop a unified theory of cognitive capacity that can mathematically predict the speed and accuracy of decision making as a function of the nature, number, and complexity of the events to which people must attend and respond. The project will be of benefit to those involved in the design and evaluation of systems and to policy makers and safety experts responsible for the legislation surrounding their use. We will communicate our results through media and via our interdisciplinary links with engineers and real-time system designers.

ARC National Competitive Grants · FY 2024 · 2024-01

A unifying model for ion exchange membranes – towards a low carbon future. Polymeric ion exchange membranes are key to emerging renewable energy systems and bioprocessing applications. Advances in this field are currently impeded by a focus on their performance in idealised pure solutions and siloed research. This project aims to draw together fundamental and applied research to develop an innovative, unifying model for the transport of both charged ions and uncharged molecules through these membranes within complex, multicomponent mixtures. The team will build on strong collaborations to drive uptake of the new model within the clean energy and CO2 reduction sectors to advance the abatement of Australian emissions; and will prepare young researchers for a role within these emerging fields. Field of research: 4004 - Chemical Engineering A low emission future for Australia will require the use of a range of electrochemical devices. These include the electrolysers used for hydrogen production, the fuel cells used for electrical energy generation and the batteries used for energy storage. Electrochemical reactors will transform carbon dioxide into chemicals. Fermentation will be used to convert biomass into solvents, chemicals and pharmaceuticals with electrodialysis used downstream of these reactors to purify the products. All of these systems use polymeric ion-exchange membranes that are not well understood. This project will combine experimental information on membrane performance and new mathematical models into computer programs that can be used by both Australian researchers and industry. The research results and computer programs will be made broadly available through the research team’s extensive industrial networks, particularly in the fields of pharmaceutical, renewable fuel and dairy product manufacture. Commercial and economic benefits will flow to the Australian industries that adopt project results by improving system designs and optimizing operating protocols. Companies will have higher productivity through improved efficiencies. Costs will be reduced through improved decisions and better usage of membranes. Importantly, the Australia environment will benefit from reduced carbon emissions through greater use of renewable energy and biomass.

ARC National Competitive Grants · FY 2024 · 2024-01

Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pathogen and mitochondrial biology and advanced cell biology tools. With most of the effector proteins yet to be characterised, benefits from the project will be to reveal specifically how these target mitochondria, and more broadly, how bacterial pathogens manipulate organelles for their survival. Field of research: 3101 - Biochemistry and Cell Biology Legionnaires disease, a severe form of pneumonia, is caused by the bacterium Legionella pneumophila. Legionella replicate inside human cells by introducing a wide range of proteins (over 300 ‘effector proteins’) into the cell. Effector proteins hijack the cells: overriding normal cell functions and causing disease. Research suggests that certain Legionella effector proteins target mitochondria. Mitochondria are complex, dynamic cell components affecting many key functions, including energy production. Effector proteins from other pathogens target mitochondria, but we don’t know which biochemical pathways Legionella is targeting. This study will investigate how Legionella effector proteins target mitochondria and manipulate mitochondrial functions. As all but the simplest forms of life have mitochondria, the resulting understanding of mitochondrial biology will have broad scientific application. The results will improve our understanding of bacterial and mitochondrial biology and pathogen–host interactions. In the long term, this could lead to new therapies or methods to combat Legionella and other pathogens. Trainee scientists in the project will gain technical skills in high demand in research and other disciplines, enhancing Australian research capability and contributing to community wellbeing and a strong economy. This research will be shared in public outreach including articles, news media and social media and will be presented at relevant conferences.