To Describe The Regional Differences In The Innate Immune System Of The Skin Using Intra-vital Multiphoton Microscopy And Understand Its Functional Consequences In A Cutaneous Parasite Infection Model.
Funder
National Health and Medical Research Council
Funding Amount
$97,182.00
Summary
This study is the first of its kind to map the innate immune system, the body's first line of defence, in the skin - coined the "immune atlas". Researchers have shown regional differences in innate immune cells which could explain how infections develop at different sites of the body. Although they have shown this in a cutaneous leishmaniasis model, a parasite endemic in most parts of the world, it may have implications also for inflammatory skin conditions such as eczema or psoriasis.
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: DE120101340
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Subversion of innate immune responses by pathogenic Escherichia coli. This project will determine how bacteria that cause diarrhoeal diseases prevent the immune system from signalling efficiently. It will provide important information not only about how the bacteria establish disease, but also provide insight into the host response in the early stages of infection.
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100070
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with gre ....An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with greater sensitivity and in a broader range of tissues and organs. This will provide the opportunity for novel insights into numerous immunological and host-microbe interactions.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.