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Exploring evolvability: its causes, consequences and practical applications in a changing environment. Are some species better able to adapt to a changing world? This question has been the focus of theoretical debate, but, as the scale of current environmental change becomes apparent, it has increasing practical importance, because it concerns the ability of biological communities to respond to climate change and the potential for agriculture to adapt a changing landscape. This project is the fi ....Exploring evolvability: its causes, consequences and practical applications in a changing environment. Are some species better able to adapt to a changing world? This question has been the focus of theoretical debate, but, as the scale of current environmental change becomes apparent, it has increasing practical importance, because it concerns the ability of biological communities to respond to climate change and the potential for agriculture to adapt a changing landscape. This project is the first of its kind, because it translates theoretical concepts into practical information needed for the development of salt-tolerant crops, new strategies for avoiding the growing problem of resistance in parasites, and new ways of detecting biological communities at risk of extinction and invasion. Read moreRead less
Enhancing plant photosynthesis by engineering the carbon dioxide (CO2)-fixing enzyme Rubisco. Improving the ability of crops to use water, sunlight and fertiliser more efficiently would have economic benefits for Australia and ease the environmental impacts associated with agricultural practices. Photosynthesis research has confirmed that such improvements are theoretically possible by enhancing the efficiency of the protein, Rubisco, which initiates the conversion of carbon dioxide into carbon ....Enhancing plant photosynthesis by engineering the carbon dioxide (CO2)-fixing enzyme Rubisco. Improving the ability of crops to use water, sunlight and fertiliser more efficiently would have economic benefits for Australia and ease the environmental impacts associated with agricultural practices. Photosynthesis research has confirmed that such improvements are theoretically possible by enhancing the efficiency of the protein, Rubisco, which initiates the conversion of carbon dioxide into carbon compounds required for growth. The biotechnological research proposed here uses unique capabilities to improve our understanding of structural features in Rubisco that influence its assembly and functional efficiency in plants. This knowledge will pave the way for transplanting more efficient Rubisco into crops to improve their growth.Read moreRead less
Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides ....Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and new tools for Australian industries.Read moreRead less
Linkages between productivity and consistent behavioural traits in fish: implications for harvesting, climate impacts, and selective breeding for aquaculture. The extent to which behavior, growth and reproduction are genetically linked in fish populations is unknown, but critical for predicting the impacts of fish harvesting and climate warming, and developing fish stains for aquaculture. If strongly linked, fish harvest will always remove aggressive, large and productive fish, requiring their p ....Linkages between productivity and consistent behavioural traits in fish: implications for harvesting, climate impacts, and selective breeding for aquaculture. The extent to which behavior, growth and reproduction are genetically linked in fish populations is unknown, but critical for predicting the impacts of fish harvesting and climate warming, and developing fish stains for aquaculture. If strongly linked, fish harvest will always remove aggressive, large and productive fish, requiring their protection; in aquaculture, selecting for productive fish will also increase aggression-related injuries. If not strongly linked, we may be able to select for high productivity and low aggression in fish, or high productivity and low metabolism, thus reducing feed costs in aquaculture associated with aggressive behaviour leading to injury and infection, and reduced growth at warmer temperatures.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these p ....Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these populations. The goal is to understand what types of mutations are targeted by selection at the gene expression level and why.Read moreRead less
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
Quantifying the Tree of Life's Diversity with the Paleobiology Database. The Paleobiology Database is the Internet's key source of scientific data on the fossil record. It records names and classification of fossil organisms and the ages, locations, and environments of the places that yield these fossils. It has often been used to estimate the number of species existing at different points in geological time. Macquarie will house the Database as it is expanded to record evolutionary relations ....Quantifying the Tree of Life's Diversity with the Paleobiology Database. The Paleobiology Database is the Internet's key source of scientific data on the fossil record. It records names and classification of fossil organisms and the ages, locations, and environments of the places that yield these fossils. It has often been used to estimate the number of species existing at different points in geological time. Macquarie will house the Database as it is expanded to record evolutionary relationships of many species. This information will help to estimate dates of origination for major groups such as mammals and birds. It will also help to show whether mass extinctions tend to target old groups with few surviving species, which will help to predict which groups will survive the current mass extinction.Read moreRead less