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Shape-shifting birds: a novel consequence of climate change. This project aims to identify which species are affected by climate change, and whether these changes in their ecology enhance or decrease fitness and survival. Climate change is having drastic effects on animal biology, threatening many species. Recent data suggest that changes in body shape (the size of appendages) is one such effect. By studying the bills and legs of birds this project aims to investigate changes in body shape as a ....Shape-shifting birds: a novel consequence of climate change. This project aims to identify which species are affected by climate change, and whether these changes in their ecology enhance or decrease fitness and survival. Climate change is having drastic effects on animal biology, threatening many species. Recent data suggest that changes in body shape (the size of appendages) is one such effect. By studying the bills and legs of birds this project aims to investigate changes in body shape as a biological response to climate change. This project will model the predicted consequences of changes in body shape on population trends in Australian birds, enabling the prediction of which species are most threatened by climate change, and helping inform conservation priorities.Read moreRead less
Genomic diversity, tolerance and ecology of wildlife disease. This project aims to understand the regulation of viral disease by vertebrate hosts. Viruses are rapidly evolving threats to humans, agriculture and wildlife and understanding of these threats can be transformed by combining the latest genomic, ecological and immune-pathological approaches. This project expects to reveal how hosts manage the bad effects of viruses in natural populations and fill gaps in fundamental knowledge of virus- ....Genomic diversity, tolerance and ecology of wildlife disease. This project aims to understand the regulation of viral disease by vertebrate hosts. Viruses are rapidly evolving threats to humans, agriculture and wildlife and understanding of these threats can be transformed by combining the latest genomic, ecological and immune-pathological approaches. This project expects to reveal how hosts manage the bad effects of viruses in natural populations and fill gaps in fundamental knowledge of virus-host evolution. Anticipated benefits include improved management, risk assessment and decision-making for animal disease and biosecurity in Australia and globally.Read moreRead less
Evolution and specificity of alternative splicing in plants. This project aims to elucidate fundamental principles of alternative splicing, a basic mechanism that plays a vital role in several biological processes across all organisms. Plants are highly effective in adapting to varied environmental, seasonal and climatic conditions and this project aims to uncover how alternative splicing contributes to regulation of gene expression in response to developmental and environmental cues. Uncovering ....Evolution and specificity of alternative splicing in plants. This project aims to elucidate fundamental principles of alternative splicing, a basic mechanism that plays a vital role in several biological processes across all organisms. Plants are highly effective in adapting to varied environmental, seasonal and climatic conditions and this project aims to uncover how alternative splicing contributes to regulation of gene expression in response to developmental and environmental cues. Uncovering the underlying mechanisms of alternative splicing will not only advance fundamental knowledge, but also has the potential to provide tools and technologies through which sensitivities of plants to environmental stress can be potentially manipulated to benefit agriculture.Read moreRead less
The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unortho ....The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unorthodox antigen recognition. Thus, the proposal will significantly advance our understanding of, and establish new paradigms around, the regulation of T cell activation. Expected long term benefits outside the scope of this proposal include improved immunotherapies and vaccines designed to elicit or suppress T cell responses.Read moreRead less
How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project inc ....How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project include discovery of mechanisms general to cytokine signalling and new approaches to investigate cytokine biology. This new knowledge will benefit efforts to understand and modulate cytokine signalling in animals and humans, with future impacts in the agriculture, veterinary, and health sectors.Read moreRead less
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
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All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and ....All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants. Read moreRead less
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less
Pore-forming toxins: more than one way to make a hole. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. The outcomes could reveal novel mechanisms general to these proteins and provid ....Pore-forming toxins: more than one way to make a hole. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants.
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The structural basis for defensin-mediated membrane attack. This project aims to define how the innate defense proteins called defensins attack target membranes to cause cells to burst and die. It is often said that attack is the best form of defense, and the immune systems of plants and animals will often target the cell membranes of microbes and other pathogens to defend themselves. This project will identify the precise molecular mechanism underlying defensin activity, and clarify how ligand ....The structural basis for defensin-mediated membrane attack. This project aims to define how the innate defense proteins called defensins attack target membranes to cause cells to burst and die. It is often said that attack is the best form of defense, and the immune systems of plants and animals will often target the cell membranes of microbes and other pathogens to defend themselves. This project will identify the precise molecular mechanism underlying defensin activity, and clarify how ligand recognition and subsequent multimerisation leads to target membrane lysis. The project will establish the fundamental mechanisms regulating antimicrobial defense systems based on small proteins, and define a conceptual framework for the action of defensins to develop strategies to combat fungal infections.Read moreRead less