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
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less
Combating invading DNA: a process conserved in evolution? Cells of our body defend against foreign genetic material, or DNA, which indicates an infection or invading DNA capable of causing mutation. These defences are so important that several layers have developed during evolution, and this project compares the responses of different organisms to foreign DNA.
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.
Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM re ....Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM remodelling. Previous studies have developed a unique mouse model of childhood asthma and discovered the molecular mechanism by which this tissue tropism develops in response to virus infection. This project will identify new targets for immunomodulation and design new biologics to block ASM remodelling and the deleterious effects of respiratory virus infection in asthmatic subjects. Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
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
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: DE130101504
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
An investigation into evolution and diversity within an innate immune recognition system. The innate immune system, which is critical for the host to combat infection, comprises a host of components that specifically recognise microbial products. This project is aimed at understanding the evolution and specificity underpinning a receptor family that is centrally involved in innate immunity.
Discovery Early Career Researcher Award - Grant ID: DE130100537
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neural regulation of immunity following brain injury. Following a brain injury, the brain tries to protect itself by blocking all inflammation. However, this renders the host with impaired immunity and increased risks to infections. The project aims to delineate the mechanisms behind this response, with the expected outcome of highlighting the important interplay between the nervous and immune system.