Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mec ....Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mechanistic insights into the molecular processes that control neuronal homeostatic responses. This will elucidate how neural plasticity and network stability are maintained, a process that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting ....Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting them in mice, testing for developmental, cognitive and motor effects, and characterising the structures with which they are associated. The results of the project are expected to open new vistas in neuroscience, contributing to understanding the molecular basis of brain function and the 'dark matter' of the genome.Read moreRead less
Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance ....Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance mediated by these host factors. A detailed understanding of the molecular interactions between plant viruses and their host will enable new, robust and more effective forms of resistance to be engineered. This work therefore has economic and environmental implications for agricultural productivity in Australia. Read moreRead less
Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations t ....Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations that optimise plant yield and fitness will be defined and explored in other, more complex, cereals such as wheat. Expected outcomes will be fundamental breakthroughs in understanding how plants respond to, and buffer, the effects of heat to lead to translational breeding strategies that bolster grain yield.Read moreRead less
From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this proj ....From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this project include new manufacturing processes for chemicals and foods, discovery of novel metabolism in yeast, and enhanced collaboration between Australia, Denmark, and the United States. This Project will provide benefits through sustainable bio-manufacturing, new economic activity, and reduced greenhouse gas emissions.Read moreRead less
Cellular Ageing: Is the Plasma Membrane the Control Hub? This project aims to determine whether the plasma membrane lipid composition is a major driver of cellular ageing. It expects to generate new knowledge in the molecular mechanism of cellular ageing, utilising our team’s deep expertise in lipid biology, bioinformatics, biophysics, extracellular vesicle biology and cellular ageing. Expected outcomes include the identification of novel cellular ageing markers and anti-ageing targets while als ....Cellular Ageing: Is the Plasma Membrane the Control Hub? This project aims to determine whether the plasma membrane lipid composition is a major driver of cellular ageing. It expects to generate new knowledge in the molecular mechanism of cellular ageing, utilising our team’s deep expertise in lipid biology, bioinformatics, biophysics, extracellular vesicle biology and cellular ageing. Expected outcomes include the identification of novel cellular ageing markers and anti-ageing targets while also cementing long-standing partnerships and fostering new interdisciplinary collaborations. This cellular ageing study will provide novel insights into the basic principles of cellular behaviour, e.g. growth, differentiation, communication and death, reinforcing Australia’s leadership in biological science.Read moreRead less
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less