Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less
Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of ....Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of way in which respiratory gene expression is controlled in bacterial species for which Escherichia coli is not a suitable model. Read moreRead less
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Discovery Early Career Researcher Award - Grant ID: DE200100778
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
Mapping the neural circuits that underlie emotional learning. This project aims to understand the precise neural circuits that mediate the formation of emotional memories. Recent findings have identified a novel complexity in these circuits and the goal of this proposal is to resolve the underlying mechanism that drives emotional memories. In detail, this project will combine state of the art dual- optical stimulation techniques combined with behaviour-dependent tagging of neurons to investigate ....Mapping the neural circuits that underlie emotional learning. This project aims to understand the precise neural circuits that mediate the formation of emotional memories. Recent findings have identified a novel complexity in these circuits and the goal of this proposal is to resolve the underlying mechanism that drives emotional memories. In detail, this project will combine state of the art dual- optical stimulation techniques combined with behaviour-dependent tagging of neurons to investigate the precise brain circuits linked to emotional learning, an approach that also allows knowledge transfer to other research fields. Expected outcomes and benefits of the project is a significant shift in our understanding of the neural mechanisms that underlie emotional learning.Read moreRead less
Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101300
Funder
Australian Research Council
Funding Amount
$423,711.00
Summary
Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills inva ....Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills invading bacteria via newly discovered structures made by dying macrophages called extracellular traps. Insight we gain by interrogating this immune cell signalling pathway, called the non-canonical inflammasome, will add valuable knowledge to our fundamental understanding of mammalian inflammation and anti-microbial responses
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.
An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enha ....An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enhance our understanding of the intersection between ion pumps and viruses.Read moreRead less