UNIVERSITY OF MELBOURNE

ARC National Competitive Grants · FY 2023 · 2023-01

Heavy Metal Chemistry Goes Nuclear: Radioactive Rhenium and Terbium Agents. This project aims to make fundamental advances in the basic knowledge of the bioinorganic chemistry of radioactive metals that have the potential to be used in the future as radioactive drugs. Technological advances in the production of radioactive isotopes of rhenium and terbium have increased the feasibility of using these radionuclides as radioactive drugs, but their use requires new basic knowledge in their fundamental coordination chemistry. This project will develop new ways to synthesise radioactive rhenium and terbium complexes. The outcomes of this project will be an improved understanding of the coordination chemistry rhenium and terbium which is required to inform their future translation to new radiopharmaceuticals. Field of research: 3402 - Inorganic Chemistry Recent scientific and technological advances have dramatically increased the feasibility of using metallic radionuclides for the treatment of cancer. This project will the knowledge gaps in fundamental chemistry that are required to translate these new technological advances to the Advanced Manufacturing of new radiation based drugs. Radionuclides can be used to treat cancer providing they can be delivered selectively to tumour tissue once injected into a patient. This research will develop molecular cages to encapsulate a selection of newly available radionuclides. These cages will be also be attached to targeting molecules to achieve selectivity. Importantly, the new molecular agents will be stable inside the body as leakage compromises targeting and increases side effects. The new technology developed by this project, will be of interest to several Australian biopharmaceutical companies interested in the Advanced Manufacturing of these radioactive agents centralised production and distribution to hospitals in Australia and Internationally.

ARC National Competitive Grants · FY 2023 · 2023-01

How are plants responding to damage by oxidizing air pollutants? This project aims to obtain detailed understanding of the chemical processes by which the air pollutants ozone and nitrogen dioxide damage plants. Through an interdisciplinary approach involving physical organic chemistry and analytical biochemistry, this project intends to discover important reactions between plant biomolecules and air pollutants, identify biochemical mechanisms for pollution damage in crop model plants and reveal the plant defence mechanism at the molecular level. Expected outcomes include the much-needed scientific foundations to support the development of more pollution-resilient crops in the future, ultimately enabling a breakthrough for the triple challenge of environmental pollution, climate change and food security. Field of research: 3405 - Organic Chemistry A key Australian government priority is ensuring food security by developing more pollution-resilient plants. This project investigates how plants are damaged by ozone and nitrogen dioxide, two major noxious air pollutants, and uncovers the mechanisms by which plants defend themselves. By studying the interactions between plants and the polluted atmosphere, this project will, for the first time, provide detailed insights into why raising air pollution levels result in decreased crop yields, and identify traits that make plants more pollution resistant. The project will lead to new knowledge and intellectual property with significant commercial benefits for the Australian agricultural sector, which makes up 12% of Australia's GDP. Thanks to established networks through the ARC Hub for Innovative Nitrogen Fertilisers and Inhibitors, this research should inform and lead to new ARC Linkage projects and collaborations with the agricultural industry, allowing the genes involved in combatting pollution damage to be identified and tested for their function to develop more pollution-resistant crops.

ARC National Competitive Grants · FY 2023 · 2023-01

Mathematical models to connect experiments across biological scales. Understanding the function and development of organs is crucial to our understanding of fundamental biology. This project aims to address our inability to connect and understand behaviour between simple and complex biological experiments. This project expects to develop new mathematical theory and models to connect experiments across scales and complexity. Expected outcomes of this project include a new mathematical modelling framework, and advances in understanding in both biology and mathematics. This should provide significant benefits as using mathematical modelling to understand experimental connections will decrease the time- and financial- costs of performing experiments, while increasing efficiency and insight. Field of research: 4901 - Applied Mathematics It is relatively easy to study individual cells but studying whole organs like the heart or digestive tract is very resource intensive—they are much more than simply the sum of their cells. Being able to predict organ behaviour from simple experiments on cells would greatly reduce research costs and speed up experiments. This project will develop a blueprint for translating the results of experiments from one level of complexity (e.g., cell) to another (e.g., organ) by exploring the connections between simple and complex experiments. Fundamental biological experiments will inform the development of new mathematical models and theory whose predictions will then be tested. This project will advance biological and mathematical knowledge and techniques relevant to a wide range of biological applications; we will deliver new mathematical and software tools to a large academic and industrial network. The research team has experience delivering software being used worldwide in both industry and academia, and experimental standards that have been adopted by an entire field.

ARC National Competitive Grants · FY 2023 · 2023-01

A longitudinal enquiry into Chinese women graduates' post-study experience. This longitudinal study of female Chinese graduates of Australian universities will be the first to track how international education changes these women’s lives long-term. Through in-depth interviews with graduates in China and Australia, it aims to reveal the lasting benefits of an Australian education for our international graduates, providing significant insights for the recovery of Australian international education in a post-COVID world. Further, the project expects to contribute to scholarly, public and government understandings of new Chinese migrants in Australia, provide new knowledge about cultural change in the middle classes of Asia’s largest and most powerful nation, and enhance Australia’s engagement with its region. Field of research: 4702 - Cultural Studies Education is among Australia’s most valuable export commodities, contributing $37.5 billion to the economy in 2019-20, but the industry has significantly declined due to the global pandemic. By demonstrating the long-term benefits of an Australian education for our international graduates, this project will deliver important new knowledge to assist the post-COVID recovery of Australian international education. It will provide economic benefit by enabling deeper understanding of the long-term, real-world advantages of an Australian education for Chinese students, thus helping our higher education sector to recalibrate and optimise its appeal in its largest export market. In addition, consistent with the government’s concern to enhance social cohesion, the research will contribute to Australia’s national interest by providing detailed, up-to-date information available publicly to policy makers and practitioners about the social experiences, attitudes and needs of a fast-growing national population of young, skilled graduate migrants from the People’s Republic of China.

ARC National Competitive Grants · FY 2023 · 2023-01

Rethinking collaborative federalism in Australian schooling policy. The governance of schooling in the Australian federation is in flux and undergoing significant contestation, with serious questions being asked about whether national policy arrangements are fit for purpose and decision-making processes are achieving the policy aspirations of collaborative federalism. This project aims to examine how Australian governments engage in collaborative schooling reform by focussing on processes associated with the formulation of the new post-2023 National School Reform Agreement. The research will engage in ‘real time’ policy analysis, engaging with policy stakeholders to examine collaborative processes centred on the new agreement, and to consider how to improve future national decision-making processes. Field of research: 3902 - Education Policy, Sociology and Philosophy It is crucial for Australian governments to work together to produce effective policies to guide our nation’s schools, yet there is limited research on the ingredients of successful collaboration in education. This research will examine how collaboration between Australian education departments and agencies can be improved to generate better outcomes in key areas such as curriculum, teaching and assessment. The project will work directly with policymakers to examine decision-making processes linked to the new National School Reform Agreement, which is a crucial policy for shaping reforms until 2028. The project will produce practical knowledge and advice for policymakers and bring them together to co-develop reforms linked to the agreement. The research has clear benefits for Australia, as improving schooling policies is key to our social and economic prosperity in a rapidly changing global environment. Research findings will be used to inform debates about the future of schooling through media outputs and public events, and will also be of significant interest and use to policymakers in other federations.

ARC National Competitive Grants · FY 2023 · 2023-01

Improving water quality modelling by better understanding solute transport. Poor stream water quality is a critical problem in Australia and globally. Stream water quality depends directly on pathways and time taken for water to transport pollutants through catchments. Predicting these pathways is highly challenging and currently requires specialised data. This project aims to better model the movement of water from rainfall to streams, enable greatly improved use of water quality data routinely collected in Australia's catchments and thereby better predict water quality behaviour. Proposed field studies aim to support this development. The outcomes sought are improved planning and management of water quality in our rivers, lakes and estuaries, improved health of these water bodies and improved water supplies. Field of research: 3707 - Hydrology This project aims to improve the modelling of water quality of catchments in Australia. This will be achieved by addressing a long-running challenge - being able to predict the pathways and time taken for water to flow across the surface and beneath the surface of catchments into streams. This is expected to improve our understanding of and ability to predict the movement of pollutants from the land to streams, thereby improving our ability to model water quality in Australian catchments. Better modelling of water quality will support the management of water quality issues impacting our water supplies and environments such as the Great Barrier Reef, and our rivers, lakes, and estuaries nationwide. A range of government agencies lead water quality management strategies across the nation and would be the users of the improved knowledge and predictive capabilities resulting from this project. This would benefit Australians through improved environmental quality and through improved water quality in our water supplies, leading to reduced treatment costs and lower health risks.

ARC National Competitive Grants · FY 2023 · 2023-01

Cloud-climate interaction over the Great Barrier Reef and Southwest Pacific. This project aims to investigate cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The project expects to generate new knowledge in the nature and variability of the trade wind clouds, including their impact on the surface radiative budget, ocean temperatures and coral bleaching events. Potential changes of these clouds due to global warming and ensuing impacts on the environment will be studied. Expected outcomes include better modelling of the Great Barrier Reef environment and improved estimates of low-cloud feedback. This should provide significant benefits in developing warning systems for bleaching events, and regional land and water management. Field of research: 3701 - Atmospheric Sciences The Great Barrier Reef transcends economic, environmental and scientific measures, having long become one the most recognised symbols of Australia. This project aims to achieve, for the first time, a comprehensive understanding of cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The research will identify the atmospheric processes that contribute to reduced cloud cover over the region and the resulting coral bleaching events, establish the governing mechanisms of the diurnal cycle of trade wind clouds, reveal the potential response of these clouds to climate change and understand their environmental impacts. Expected outcomes include better modelling of the Great Barrier Reef environment and improved estimates of low-cloud feedback. Through community connectivity, this research should provide significant benefits in developing effective warning systems for future bleaching events, improving regional weather and climate predictions, and supporting land and water management for Queensland's coast and rainforest regions.

ARC National Competitive Grants · FY 2023 · 2023-01

Transformative simulation techniques for complex polymer networks. The study of long chain polymers like DNA using computer simulations has uncovered exciting insights over many years. Generally these have been limited to simple topologies, interactions, and environments. This project aims to develop the next generation of simulation techniques to tackle a new frontier of polymer models, including those with complex topologies like stars, knots, and links, which have hitherto been inaccessible. Expected outcomes include new simulation methods which harness modern computational clusters, leading to greater understanding of polymers with complex topologies and in complicated environments. Important elements of biological processes may be discovered, such as how polymer structure affects DNA transcription. Field of research: 4902 - Mathematical Physics Many materials are made of polymers—big molecules made up of repeating small parts. Natural polymers include silk, proteins and DNA; synthetic include nylon, plastics and Teflon. Understanding how different polymers function is key to many studies in biology, medicine and materials science. Polymer function is largely determined by their structure—sometimes the small parts are linked in a straight line, but often it is a complicated knot or web that can only be investigated with sophisticated computer simulations. This project will develop new algorithms harnessing powerful supercomputers to perform high-precision studies of complex polymer networks that could not previously be studied. Our techniques and algorithms will be open access—available to engineers and researchers developing a wide range of polymers such as those affecting how viruses replicate (and thus how their spread could be prevented). Australian industry will be able to use our findings to improve manufacturing techniques or develop new materials (such as those in corrosion-resistant paints and our plastic banknotes) and medical products.

ARC National Competitive Grants · FY 2023 · 2023-01

Sperm ciliary gating and midpiece formation – a novel player and process. We have identified CCDC112 an essential player in mammalian sperm tail development and male fertility. This project aims to define the role of CCDC112 in 1) the formation of the core to the sperm tail, the axoneme, and 2) the packaging of mitochondria into the midpiece. Within this Discovery Project we will define the mechanism(s) of CCDC112 functions and the consequences of its dysfunction. Insights from this grant will be of significance to fertility across mammals and may ultimately benefit the selection of highly fertile males within the agricultural sector. Field of research: 3215 - Reproductive Medicine Male infertility in mammals can be caused by sperm formation problems that result structural or functional defects. These defects sperm’s ability to swim through the female reproductive tract and fertilise an egg. This project addresses knowledge gaps in sperm formation, focusing on a protein (CCDC112) known to be essential in male fertility in some species. Using state-of-the-art imaging, at previously unachievable resolution, and cell biology techniques, we will investigate this protein’s role in two poorly understood processes: development of the internal structure of the sperm tail; and assembly of mitochondria—cell components that provide energy for movement—in the tail. The project will generate knowledge applicable to breeding of many agricultural species; for example, almost one-fifth of bulls have defective sperm, reducing productivity of cattle herds. Being able to ensure matings with bulls with optimal sperm structure or buy higher-quality frozen sperm for artificial insemination, will improve cattle farmers’ profitability.

ARC National Competitive Grants · FY 2023 · 2023-01

Horizontal ecological networks for understanding biodiversity maintenance. The project aims to develop new ecological theory on local diversity maintenance based on an innovative interaction network model, tested on Western Australian wildflower communities. It is novel in its focus on the complexity of species interactions and their importance to diversity maintenance in nature. This project aims to explore links between plant interaction networks and coexistence theory to provide theoretical expectations for how changes to the environment are expected to alter natural plant communities. It aims to fill theory-gap about mechanisms of multi-species coexistence, advance community ecology, and provide the theoretical foundations necessary for translating ecological theory to restoration and conservation in practice. Field of research: 3103 - Ecology Maintaining local biodiversity is vital for cultural and economic reasons, but difficult given the complexity of varying threats. Existing diversity models oversimplify the complexity of diverse natural systems, which limits their application to real-world conservation challenges. We will take a networking approach to modelling plant community responses to local environmental changes. Using field ecology studies of a threatened Western Australia plant system, we will test complex systems approaches to understanding the biology of plant community diversity. This project will fill a critical theoretical gap about the biological mechanisms allowing many plant species to live together in nature. Outcomes will include new ecological theory and novel statistical tools useful for translating theory to real-world applications across Australia. Government agencies managing parks and reserves and community groups like Bush Heritage can use the new knowledge and tools to better maintain Australia’s iconic ecosystems and biodiversity, futureproofing sectors such as Western Australia’s wildflower tourism industry.

ARC National Competitive Grants · FY 2023 · 2023-01

Nowcasting and Interpreting the Australian Economy. This project aims to investigate methods for nowcasting and interpreting the Australian economy. This is determining the current state of the economy and the factors contributing to it. This project expects to generate new knowledge on how unconventional, new, data sources and innovative methods can be used to in nowcasting and how the Australian economy can be modelled. The expected outcomes include timely new indicators of the state of the economy, and the factors contributing to it. This should provide significant benefits through informing the conduct of Australian macroeconomic policy, as the appropriate policy response depends not only on knowing the current state of the economy but understanding the economic factors underlying it. Field of research: 3802 - Econometrics Australian policy makers need accurate and timely measures of Australian economic activity and its main drivers to set policies on taxes, government spending and interest rates. Yet official data often are months old, and current economic models relying on them do not provide timely measures of the factors driving today’s economy. This project will use unconventional, new data sources and modern techniques to create a set of regularly updated, publicly available, high-frequency indicators of the current state of the Australian economy and its determinants. Innovative modelling methods will use these indicators to create a new macroeconomic model of the Australian economy that is intended to become the new benchmark. Project participants from the Australian Treasury and the Australian Bureau of Statistics will facilitate adoption of the project outcomes in Government agencies. This project will produce significant societal and economic benefits by providing Australian macroeconomic policymakers with better, timelier information to assist their decisions and understand the impacts of macroeconomic policies.

ARC National Competitive Grants · FY 2023 · 2023-01

Reading climate: Indigenous literatures, school English and sustainablity. Reading Climate aims to investigate the connections between sustainability and Indigenous knowledge in the context of school English and directly responds to imperatives for climate education and racial justice in Australian schools. It links teachers, students, authors and scholars through book clubs, exploring the potential of literature as an interdisciplinary site for knowledge building and for reimagining social and environmental futures. With partners the Stella Prize, the Australian Association for the Teaching of English, Feral Arts and VoicEd Radio, the project will develop strong collaborations between literary education, industry, and Indigenous writing, producing an open access digital resource for use in schools nationally. Field of research: 3901 - Curriculum and Pedagogy Climate education is an imperative for school systems internationally and nationally. Indigenous writers offer ways of understanding and responding to the climate crisis, but their texts, and the knowledges they represent, are yet to be effectively integrated into school curriculum areas. Taking English curriculum as a focus, this project links Indigenous literary texts, teachers, students and scholars to advance climate education in schools, building knowledge of climate and racial justice through an innovative book club approach. Responding to national commitments to ‘Closing the Gap’ and Australian curriculum priorities, this project seeks to embed Indigenous knowledges in schools nationally. Partnering with the Stella Prize, the Australian Association for the Teaching of English, Feral Arts and VoicEd Radio, the project will build collaborations across education, industry, and Indigenous writers, offering environmental, cultural, social and economic benefits through increased circulation of Indigenous texts, and a publicly available Reading Climate resource toolkit for use in Australian schools.

ARC National Competitive Grants · FY 2023 · 2023-01

The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper action on the enzyme and its partners. Expected outcomes include an analytical understanding of the molecular mechanisms of this process, and enhanced interdisciplinary collaboration between experts. Potential benefits include new strategies to intervene in copper-related disorders of aging. Field of research: 3404 - Medicinal and Biomolecular Chemistry Nutrient copper is an essential ingredient for life and plays a role in diseases like Alzheimer’s and cancer. But we know little about how copper acts within cells and why it is so important for life. We recently discovered that copper drives a system that removes damaged proteins within cells. This copper-dependent mechanism is found in humans, other mammals, fish and even flies. Using approaches unique to our laboratory, we will elaborate the precise biochemical way that copper exerts this influence. The findings from this project will be disseminated through the scientific literature, where it will be of importance to biochemistry and biology researchers, particularly those studying these pathways in normal organ development. As defective protein breakdown is implicated in major diseases, the results will also interest medical researchers studying these pathways in cancer and neurodegeneration. The findings will be relevant for future drug development, with potential to benefit the health of Australians, and bring commercial and economic benefits such as improved productivity of livestock and fisheries.

ARC National Competitive Grants · FY 2023 · 2023-01

"Painting" the 3D proteome: folding, conformation and interactions. The project aims to develop a "residue painting approach", employing novel chemical biology reagents and advanced quantitative proteomics, to monitor changes in protein folding, conformations and interactions in cells, in response to stimuli. Proteins direct almost all functions required to sustain life. The project expects to map the dynamic 3D-structures of thousands of proteins that inform the networks they are in, and of the conformations they adopt. Expected outcomes include the development of novel biotechnology tools for protein structure and function analysis, the illumination of important cell biology pathways underpinning molecular responses to stimuli and stress, and the training of our next generation of scientists. Field of research: 3101 - Biochemistry and Cell Biology Proteins are the workhorses of biology, assembling together into networks to perform molecular functions. These networks rearrange when a different function is required and when cells respond to different stimuli. These networks are essential to all life functions, so knowing how they are arranged offers great power to tweak them for particular functions and also understand errors that cause disease; this has great potential for improving crop yield, building resistance to disease in animal, plant or microbial organisms and treating disease. This project will develop new tools to provide information on protein network structures, including in live cells with thousands of networks. These tools will be of use to teams researching basic cellular function in fields as diverse as human health (e.g., cancer, Alzheimer’s disease), horticulture, agriculture, pathogens and microbiomes. The knowledge may be adopted by industries that manufacture proteins (e.g., pharmaceutical production of vaccines, hormones, protein-based therapies) and in biotechnology (e.g., building resistance to heat stress in corals or crops).

ARC National Competitive Grants · FY 2023 · 2023-01

Beyond the resource curse: redistribution and resource-led development. The project aims to improve the sustainability of resource-led development in Australia and worldwide via a novel, multi-scalar framework, co-produced with mining/Indigenous communities that connects local development outcomes with mining global production networks (GPN). It will generate new, community co-authored and policy-engaged knowledge to better attune fiscal, industry and regional policies to tackling the local resource curse. Expected outcomes include co-developed GPN theory advances; new policies for sustainable mining locality development; and more engaged mining/Indigenous communities. Significant welfare savings, social coherence, environment amelioration and cultural transformation benefits are expected. Field of research: 4406 - Human Geography Mining produces wealth for the country, but the wealth is typically not reinvested into mining towns. They often suffer from a “local resource curse”, facing acute socio-economic challenges including unaffordable housing, lack of services, environmental damage and marginalisation of Indigenous populations. This project investigates three copper mining towns in different countries—Mt Isa, Australia; Calama, Chile; and Chambishi, Zambia—to generate community co-authored, policy-engaged knowledge on how to overcome these challenges. We will combine analyses of data and current policies for local mining industries with data from in-depth interviews with government, industry and community stakeholders, and focus groups with community and Indigenous organisations. Traditional academic outputs, reports and guidelines, public presentations, workshops and a multilingual handbook will be used to inform policy. Best practice evidence-based, community-engaged policy design will empower communities and reduce welfare dependence, social discontent and environmental deterioration, even beyond the mining case studies.

ARC National Competitive Grants · FY 2022 · 2022-01

Characterization of the dark metabolome of eukaryotic cells. The project aims to investigate the full metabolic potential of a group of eukaryotic organisms using advanced analytical and computational techniques. It will identify novel metabolites and enzyme activities that are currently not predicted from genome annotations. Expected outcomes of the project include the delineation of new metabolic processes that are common to all eukaryotes, the characterization of new enzymes families, and the generation of comprehensive metabolic databases. An improved understanding of cellular metabolism will provide direct benefits in biotechnology, food production, environmental monitoring and the diagnosis and treatment of human metabolic and infectious diseases. Field of research: 0601 - Biochemistry and Cell Biology This project will provide fundamental new information on cellular metabolism that underpins all aspects of life. The work will contribute to Australia’s national interest by (1) improving our ability to model microbial metabolism and generate improved strains in the biotechnology industry, (2) improving our understanding of a wide range of human diseases, including obesity, diabetes, metabolic syndrome, (3) building capability in advanced analytical technologies in Australia, including national facilities, that underpin developments in the environmental, biotechnology and biomedical sciences, (4) providing outstanding training opportunities for higher degree students and post-doctoral researcher in advanced analytical, computational and genomic sciences and (5) building important international linkages with one of the leading centres for genomic research in North America.

ARC National Competitive Grants · FY 2022 · 2022-01

How do signals cross the cell membrane: the betacommon receptor family. This project aims to unravel missing molecular details of how a family of proteins, called the betacommon receptors, is able to signal across cell walls. This project aims to generate new knowledge about how membrane-bound receptors transmit biological signals in living organisms. Despite their fundamental importance in biology, how these proteins work remain enigmatic. Expected outcomes include discovery of novel mechanisms general to these types of protein receptors and fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this new knowledge should benefit efforts to discover novel treatments in cases where malfunctioning receptors cause diseases in animals and humans. Field of research: 0601 - Biochemistry and Cell Biology This project will provide insights into the fundamental biology of a class of proteins called cell surface receptors. Cell surface receptor proteins respond to extracellular molecular signals and regulate major cellular functions in all kingdoms of life and thus have known importance and utlised in agriculture and biotechnology. This study will focus on cytokine receptors that are particularly associated with immune defence and for which Australia has been a pioneer. The discovery of cytokines by Metcalf in the 1970s launched a new field of biology, with Australian scientists making major contributions ever since. Findings from this research provide the foundations to lead the development of engineered proteins with great importance, with potential benefits for Australia's biotechnology industry, placing Australian science at the forefront of an emerging technology. This may have significant impact on the Australian economy through spin-off companies and licensing agreements.

ARC National Competitive Grants · FY 2022 · 2022-01

Mechanisms maintaining mitochondrial copper homeostasis. This project aims to define the molecular mechanisms by which copper is trafficked and balanced within mitochondria. The project will employ an integrated biological, biochemical, biophysical and structural approach to examine the proteins which underpin the balance between the essentiality for copper and its toxicity, within this organelle. This project will deliver fundamental insights into how mitochondria contribute to and achieve cellular metal homeostasis, in addition to molecular explanations for how faults in this process result in mitochondrial defects. Major benefits include research training, strengthened international linkages and fundamental insights into mitochondrial biochemistry. Field of research: 0601 - Biochemistry and Cell Biology Living cells contain tiny organelles called mitochondria that generate energy. This energy powers the multitude of chemical reactions taking place in cells at any one time. Many of these reactions require metal ions in the chemical processes that are vital to cells in all forms of life. This study will reveal how copper, an essential metal, is balanced within cells to optimally contribute to these chemical reactions. This knowledge is key to defining the chemical processes that support living systems and in understanding how defects in metals can lead to dysfunction in the cell. The research integrates biological, biochemical, biophysical and structural technologies to examine proteins and their interactions that underpin cell function. Australia will benefit from this interdisciplinary emphasis by creating multi-skilled students and trainees able to tackle other complex problems at the interface between disparate scientific disciplines. These skills will particularly impact on agriculture, food science and medicine.

ARC National Competitive Grants · FY 2022 · 2022-01

The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will be the first to comprehensively advance our understanding of the unique role of sex hormones in shaping the adolescent female brain. It will provide critical understanding of how individual differences in hormonal factors increase risk for emotional problems in females, and inform treatment strategies. Field of research: 1701 - Psychology Emotional problems (e.g., anxiety, depression), which are over-represented in females, are the leading cause of morbidity during adolescence and contribute to 60% of total disease burden in Australian adolescents. Research in adult females shows that sex hormones that fluctuate over the menstrual cycle impact emotional functioning by causing changes in the brain. This project will investigate how these hormones affect the brain during adolescence. Findings will contribute to a better understanding of the biological drivers of emotional problems in adolescence, and inform the development of specialised interventions for the pubertal period. This project will provide Australian health professionals, researchers and educators with new knowledge regarding the determinants of female adolescents’ emotional behaviours and problems. The impacts of this research will have economic and societal benefits; for example, being better able to detect and treat emotional problems in adolescents will reduce societal financial burdens.

ARC National Competitive Grants · FY 2022 · 2022-01

Investigating Wnt signaling during human nephron commitment and patterning. Aims: To use gene edited stem cell lines that display cell location, identity and cell state to map human kidney tissue formation in the laboratory. By monitoring how each cell responds to those around it across time and space, we will for the first time map the formation of kidney tissue in the dish. Significance: Understanding how stem cells form a tissue will help us to improve and control the process. This is key to advancing tissue engineering. Expected outcomes: The proposal will pioneer state-of-the-art imaging, gene editing and machine learning approaches, generating models of human development that are currently unavailable. Benefits: This understanding will guide the development of novel approaches to tissue engineering. Field of research: 0601 - Biochemistry and Cell Biology This proposal will use genetically manipulated stem cells to map formation of kidney tissue in a culture dish. Understanding how cells communicate to form a tissue will enable the process to be controlled and manipulated in biotechnology. The long-term applications of the knowledge gained relate to the burgeoning biotechnology sector, particularly around tissue engineering. For example, while kidney disease is a major economic burden, and particularly affects indigenous Australians, the project outcomes will be relevant for all organs in humans and livestock. The project therefore has significant potential to contribute to Australia’s economic, commercial and social interests. The ability to generate biological tissues in a controlled and reproducible way has the potential to drive economic gain through commercialisation of the intellectual property. Outcomes will also include the development of cutting edge technology, enhanced international research reputation and potential commercial partnerships.

ARC National Competitive Grants · FY 2022 · 2022-01

New insights on the forcing of Quaternary ice-age terminations. This project investigates the period when Earth's climate last experienced a major step change. Using novel techniques, it combines information from an exceptional archive of cave deposits and ocean sediments to precisely determine the timing of ice-age cycles. The results will provide the first robust test of hypotheses proposed to explain these cycles, leading to refinements in the astronomical theory of the ice ages. They will also provide an essential reference record of Northern Hemisphere ice-sheet history, which will complement data from forthcoming Antarctic ice cores. Together, this will better contextualise current and projected greenhouse warming. Field of research: 0406 - Physical Geography and Environmental Geoscience This project will produce new data to help us understand why Earth's climate took its last major turn, which occurred about one million years ago. This was a time when natural climate cycles became longer and shifted dramatically to a larger amplitude. Greenhouse warming is currently pushing our climate towards the next major turn, with potentially profound consequences for Australian society, economy and environment over the coming decades. Interrogating past turning points is fundamentally important for placing current climate change into context. The results from our project will reveal the links between natural external forcing (such as variations in the Sun's energy), the internal feedbacks between the atmosphere, ice sheets and oceans, and major episodes of environmental change. This will ultimately lead to a better preparedness of the Australian and international communities to tackle the current climate change problem.

ARC National Competitive Grants · FY 2022 · 2022-01

Millennial climate change in southern Australia during the Last Glacial. Abrupt warming and cooling events were a persistent feature of Earth's most recent climate cycle. Surprisingly, little is known of how these events affected the climate of Australia. This project will produce precisely dated reconstructions of rainfall and temperature trends in southern Australia during these events. These new terrestrial and ocean data will be compared with model simulations to determine how rapidly abrupt climate perturbations in the Northern Hemisphere reached our region, and the processes by which this occurred. The results will advance theory on how abrupt climate change propagates globally and provide a long-awaited climatic context for capstone events in Australia's natural history. Field of research: 0406 - Physical Geography and Environmental Geoscience The data produced in this project will test how well climate models can simulate the effects of abrupt climate change on southern Australia, where 75% of our population resides. Abrupt climate change is a potential consequence of global warming. Australia is particularly vulnerable given its susceptibility to climate extremes. Floods and droughts in regions such as southern Australia, where much of our food is grown, bring devastating economic, environmental and human costs. Their effects are firmly implanted in the national psyche. Our data-model comparisons will help us understand the atmospheric and ocean circulation adjustments that accompany abrupt climate change, and highlight areas where model improvements are needed. This will ultimately give greater confidence in the accuracy of model projections of future climate, which will benefit all Australians.

ARC National Competitive Grants · FY 2022 · 2022-01

Topology in seven dimensions. Aims: The project aims to give a complete classification of a certain class of 7-dimensional spaces; namely simply-connected spin 7-manifolds. We also present related programs classify G_2-structures on 7-manifolds. Significance: the proposed classification will be a signature achievement in the topology of manifolds, with applications likely in both geometry and mathematical physics. Expected outcomes: The project will produce a series of papers published in high quality journals and enhanced scientific collaboration between Australia and the United Kingdom. Benefits: The project will enhance Australia's research reputation by producing excellent research in a field not historically represented in the country. Field of research: 0101 - Pure Mathematics Research in the fundamental mathematical sciences underpins many developments in applied sciences and engineering, many of which would often not be possible without an appropriate mathematical framework. This project will develop a new classification mathematical structure with known applications in mathematical physics. A strong mathematical research community has historically been essential to educating and attracting the scientists and engineers crucial to economic success in a changing world, thereby laying the foundation for future national economic and social benefits for Australia. The project will also benefit Australia through supporting international scientific collaboration and crucially maintain and enhance Australia's pure research capability.

ARC National Competitive Grants · FY 2022 · 2022-01

The Politicisation of Free Trade Agreements in the US, EU and Australia. This project aims to investigate why free trade agreements are increasingly politicised in liberal democracies. Politicisation has generated widespread public backlash against free trade but has also varied across agreements and countries. The project uses a novel comparative framework to explain the economic and political factors determining free trade agreement politicisation in the US, EU and Australia, actors with the most trade deals. Expected outcomes include new understandings of public backlash against free trade and globalisation. Expected benefits include recommendations on including civil society in trade policy-making and allaying populist protectionism, without jeopardising economic openness and the rules-based liberal order. Field of research: 1606 - Political Science Australia has championed trade liberalisation by signing many free trade deals. It has benefited from the rules-based global trade system, gaining tremendous economic prosperity and stability. This system has recently come under attack from populist protectionist forces across the world. This development has led to the politicisation of trade agreements in many developed economies, including Australia, endangering the liberal economic order. Policy-makers' responses have often been slow and reactive. By identifying the causes of public backlash against trade agreements and drawing lessons from the EU and the US, this project will help Australian political and social actors, making recommendations on ensuring that trade policy works for all. Since Australia is a major stakeholder in the rules-based order, making trade deals accepted by the public and civil society is paramount to its future prosperity and global leadership role. The findings and recommendations will help Australian policymakers and their like-minded international partners to protect the liberal order from the rising protectionist tide.

ARC National Competitive Grants · FY 2022 · 2022-01

Cultural knowledge in China’s Belt and Road Initiative. This project aims to clarify how the international expansion of China’s Belt and Road Initiative (BRI) is shaped by cultural factors alongside economic and political diplomacy. New knowledge about the interaction of local priorities with global networks is drawn from ethnographic data gathered in China and its food suppliers Argentina, Brazil and Australia. It hypothesises that such interactions are mediated by individuals and institutions who research and communicate local ecological and territorial knowledge. Expected outcomes include academic publications, policy papers, and media pieces. Benefits include filling a gap in network theory, an updated approach to research ethics, and improved national capacity to manage BRI’s impact. Field of research: 1601 - Anthropology The Belt and Road Initiative (BRI) is the Chinese government’s signature platform for expanding outbound investment and securing the supply of natural resources. It encompasses 80 countries, one third of global trade and $350 billion in investments by the mid-2020s. The project compares how Australia and two of China’s other leading food suppliers (Argentina and Brazil) are assessing BRI’s risks and benefits. It does this in two ways: (i) by clarifying how key individuals research and communicate local territorial and environmental concerns to shape BRI networks, and (ii) by evaluating how these individuals can more ethically and openly manage political pressures. The project supports Australia’s Science and Research Priority “Food” by explaining how the interests of Chinese investors and local producers may overlap or diverge. It achieves this through publications and media engagements that clarify the risks and benefits of BRI’s expansion. This knowledge will benefit Australian policymakers, researchers, small farmers and agriculture operators.