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
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.
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
How filopodia connect macrophages to the outside world. Fundamental to life is the ability of cells to sense their surroundings and respond accordingly. This project aims to generate a biological understanding of how certain immune cells carry out such processes, thus enabling them to combat infections.
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
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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Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massi ....Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massive translation of the scaffolding protein Tau. More importantly, the activation of this cascade is Tau-dependent. This project aims to determine how Tau activates this pathway, and to decipher the physiological role of the Tau/Fyn/Tau feedback loop. This will inform our understanding of the molecular regulation of learning and memory.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